国际兽医癫痫工作组共识建议:欧洲犬癫痫的药物治疗丨伊匹妥因丨翻译节选

<img data-src="
Warning: curl_setopt_array(): Unable to create temporary file. in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php on line 59
GuzzleHttp\Exception\RequestException: cURL error 0: The connection unexpectedly failed without providing an error. The request would have been retried, but attempting to rewind the request body failed. Exception: RuntimeException: Stream is not seekable in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\psr7\src\Stream.php:204
Stack trace:
#0 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\psr7\src\Stream.php(193): GuzzleHttp\Psr7\Stream->seek(0)
#1 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(517): GuzzleHttp\Psr7\Stream->rewind()
#2 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(152): GuzzleHttp\Handler\CurlFactory::retryFailedRewind(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Array)
#3 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(105): GuzzleHttp\Handler\CurlFactory::finishError(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#4 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(201): GuzzleHttp\Handler\CurlFactory::finish(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#5 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(130): GuzzleHttp\Handler\CurlMultiHandler->processMessages()
#6 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(145): GuzzleHttp\Handler\CurlMultiHandler->tick()
#7 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Handler\CurlMultiHandler->execute(true)
#8 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#9 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(269): GuzzleHttp\Promise\Promise->waitIfPending()
#10 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(226): GuzzleHttp\Promise\Promise->invokeWaitList()
#11 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#12 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(67): GuzzleHttp\Promise\Promise->wait()
#13 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Promise\Coroutine->GuzzleHttp\Promise\{closure}(true)
#14 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#15 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#16 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(103): GuzzleHttp\Promise\Promise->wait(true)
#17 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(77): GuzzleHttp\Promise\Coroutine->wait()
#18 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(153): GuzzleHttp\Command\ServiceClient->execute(Object(GuzzleHttp\Command\Command))
#19 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(269): GuzzleHttp\Command\ServiceClient->__call(‘PutObject’, Array)
#20 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(321): Qcloud\Cos\Client->__call(‘putObject’, Array)
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(36): Qcloud\Cos\Client->upload(‘chonwuleyuan-12…’, ‘415ee155fa5ed10…’, Object(GuzzleHttp\Psr7\Stream))
#22 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘415ee155fa5ed10…’)
#23 {main} (see https://curl.haxx.se/libcurl/c/libcurl-errors.html) in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php:201
Stack trace:
#0 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(524): GuzzleHttp\Handler\CurlFactory::createRejection(Object(GuzzleHttp\Handler\EasyHandle), Array)
#1 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(152): GuzzleHttp\Handler\CurlFactory::retryFailedRewind(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Array)
#2 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(105): GuzzleHttp\Handler\CurlFactory::finishError(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#3 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(201): GuzzleHttp\Handler\CurlFactory::finish(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#4 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(130): GuzzleHttp\Handler\CurlMultiHandler->processMessages()
#5 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(145): GuzzleHttp\Handler\CurlMultiHandler->tick()
#6 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Handler\CurlMultiHandler->execute(true)
#7 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#8 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(269): GuzzleHttp\Promise\Promise->waitIfPending()
#9 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(226): GuzzleHttp\Promise\Promise->invokeWaitList()
#10 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#11 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(67): GuzzleHttp\Promise\Promise->wait()
#12 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Promise\Coroutine->GuzzleHttp\Promise\{closure}(true)
#13 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#14 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#15 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(103): GuzzleHttp\Promise\Promise->wait(true)
#16 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(77): GuzzleHttp\Promise\Coroutine->wait()
#17 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(153): GuzzleHttp\Command\ServiceClient->execute(Object(GuzzleHttp\Command\Command))
#18 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(269): GuzzleHttp\Command\ServiceClient->__call(‘PutObject’, Array)
#19 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(321): Qcloud\Cos\Client->__call(‘putObject’, Array)
#20 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(36): Qcloud\Cos\Client->upload(‘chonwuleyuan-12…’, ‘415ee155fa5ed10…’, Object(GuzzleHttp\Psr7\Stream))
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘415ee155fa5ed10…’)
#22 {main}” width=”1227″ height=”47″>
<img data-src="
Warning: curl_setopt_array(): Unable to create temporary file. in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php on line 59
GuzzleHttp\Exception\RequestException: cURL error 0: The connection unexpectedly failed without providing an error. The request would have been retried, but attempting to rewind the request body failed. Exception: RuntimeException: Stream is not seekable in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\psr7\src\Stream.php:204
Stack trace:
#0 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\psr7\src\Stream.php(193): GuzzleHttp\Psr7\Stream->seek(0)
#1 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(517): GuzzleHttp\Psr7\Stream->rewind()
#2 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(152): GuzzleHttp\Handler\CurlFactory::retryFailedRewind(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Array)
#3 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(105): GuzzleHttp\Handler\CurlFactory::finishError(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#4 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(201): GuzzleHttp\Handler\CurlFactory::finish(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#5 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(130): GuzzleHttp\Handler\CurlMultiHandler->processMessages()
#6 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(145): GuzzleHttp\Handler\CurlMultiHandler->tick()
#7 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Handler\CurlMultiHandler->execute(true)
#8 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#9 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(269): GuzzleHttp\Promise\Promise->waitIfPending()
#10 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(226): GuzzleHttp\Promise\Promise->invokeWaitList()
#11 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#12 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(67): GuzzleHttp\Promise\Promise->wait()
#13 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Promise\Coroutine->GuzzleHttp\Promise\{closure}(true)
#14 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#15 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#16 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(103): GuzzleHttp\Promise\Promise->wait(true)
#17 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(77): GuzzleHttp\Promise\Coroutine->wait()
#18 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(153): GuzzleHttp\Command\ServiceClient->execute(Object(GuzzleHttp\Command\Command))
#19 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(269): GuzzleHttp\Command\ServiceClient->__call(‘PutObject’, Array)
#20 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(321): Qcloud\Cos\Client->__call(‘putObject’, Array)
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(36): Qcloud\Cos\Client->upload(‘chonwuleyuan-12…’, ‘ec03b2b3e8240a2…’, Object(GuzzleHttp\Psr7\Stream))
#22 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘ec03b2b3e8240a2…’)
#23 {main} (see https://curl.haxx.se/libcurl/c/libcurl-errors.html) in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php:201
Stack trace:
#0 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(524): GuzzleHttp\Handler\CurlFactory::createRejection(Object(GuzzleHttp\Handler\EasyHandle), Array)
#1 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(152): GuzzleHttp\Handler\CurlFactory::retryFailedRewind(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Array)
#2 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(105): GuzzleHttp\Handler\CurlFactory::finishError(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#3 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(201): GuzzleHttp\Handler\CurlFactory::finish(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#4 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(130): GuzzleHttp\Handler\CurlMultiHandler->processMessages()
#5 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(145): GuzzleHttp\Handler\CurlMultiHandler->tick()
#6 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Handler\CurlMultiHandler->execute(true)
#7 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#8 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(269): GuzzleHttp\Promise\Promise->waitIfPending()
#9 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(226): GuzzleHttp\Promise\Promise->invokeWaitList()
#10 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#11 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(67): GuzzleHttp\Promise\Promise->wait()
#12 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Promise\Coroutine->GuzzleHttp\Promise\{closure}(true)
#13 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#14 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#15 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(103): GuzzleHttp\Promise\Promise->wait(true)
#16 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(77): GuzzleHttp\Promise\Coroutine->wait()
#17 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(153): GuzzleHttp\Command\ServiceClient->execute(Object(GuzzleHttp\Command\Command))
#18 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(269): GuzzleHttp\Command\ServiceClient->__call(‘PutObject’, Array)
#19 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(321): Qcloud\Cos\Client->__call(‘putObject’, Array)
#20 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(36): Qcloud\Cos\Client->upload(‘chonwuleyuan-12…’, ‘ec03b2b3e8240a2…’, Object(GuzzleHttp\Psr7\Stream))
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘ec03b2b3e8240a2…’)
#22 {main}” width=”627″ height=”359″>

国际兽医癫痫工作组共识建议:欧洲犬癫痫的药物治疗

Sofie F.M. Bhatti1*, Luisa De Risio2 , Karen Mu~nana3 , Jacques Penderis4 , Veronika M. Stein5 , Andrea Tipold5 , Mette Berendt6 , Robyn G. Farquhar7 , Andrea Fischer8 , Sam Long9 , Wolfgang L”oscher10, Paul J.J. Mandigers11, Kaspar Matiasek12, Akos Pakozdy13, Edward E. Patterson14, Simon Platt15, Michael Podell16, Heidrun Potschka17, Clare Rusbridge18,19 and Holger A. Volk20

翻译 By @苏苏苏苏乔

校正 By @宠物神经科医生高健

Imepitoin 伊匹妥因

<img data-src="
Warning: curl_setopt_array(): Unable to create temporary file. in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php on line 59
GuzzleHttp\Exception\RequestException: cURL error 0: The connection unexpectedly failed without providing an error. The request would have been retried, but attempting to rewind the request body failed. Exception: RuntimeException: Stream is not seekable in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\psr7\src\Stream.php:204
Stack trace:
#0 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\psr7\src\Stream.php(193): GuzzleHttp\Psr7\Stream->seek(0)
#1 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(517): GuzzleHttp\Psr7\Stream->rewind()
#2 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(152): GuzzleHttp\Handler\CurlFactory::retryFailedRewind(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Array)
#3 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(105): GuzzleHttp\Handler\CurlFactory::finishError(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#4 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(201): GuzzleHttp\Handler\CurlFactory::finish(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#5 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(130): GuzzleHttp\Handler\CurlMultiHandler->processMessages()
#6 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(145): GuzzleHttp\Handler\CurlMultiHandler->tick()
#7 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Handler\CurlMultiHandler->execute(true)
#8 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#9 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(269): GuzzleHttp\Promise\Promise->waitIfPending()
#10 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(226): GuzzleHttp\Promise\Promise->invokeWaitList()
#11 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#12 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(67): GuzzleHttp\Promise\Promise->wait()
#13 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Promise\Coroutine->GuzzleHttp\Promise\{closure}(true)
#14 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#15 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#16 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(103): GuzzleHttp\Promise\Promise->wait(true)
#17 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(77): GuzzleHttp\Promise\Coroutine->wait()
#18 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(153): GuzzleHttp\Command\ServiceClient->execute(Object(GuzzleHttp\Command\Command))
#19 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(269): GuzzleHttp\Command\ServiceClient->__call(‘PutObject’, Array)
#20 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(321): Qcloud\Cos\Client->__call(‘putObject’, Array)
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(36): Qcloud\Cos\Client->upload(‘chonwuleyuan-12…’, ‘e871b9dcd3356f7…’, Object(GuzzleHttp\Psr7\Stream))
#22 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘e871b9dcd3356f7…’)
#23 {main} (see https://curl.haxx.se/libcurl/c/libcurl-errors.html) in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php:201
Stack trace:
#0 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(524): GuzzleHttp\Handler\CurlFactory::createRejection(Object(GuzzleHttp\Handler\EasyHandle), Array)
#1 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(152): GuzzleHttp\Handler\CurlFactory::retryFailedRewind(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Array)
#2 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(105): GuzzleHttp\Handler\CurlFactory::finishError(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#3 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(201): GuzzleHttp\Handler\CurlFactory::finish(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#4 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(130): GuzzleHttp\Handler\CurlMultiHandler->processMessages()
#5 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(145): GuzzleHttp\Handler\CurlMultiHandler->tick()
#6 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Handler\CurlMultiHandler->execute(true)
#7 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#8 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(269): GuzzleHttp\Promise\Promise->waitIfPending()
#9 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(226): GuzzleHttp\Promise\Promise->invokeWaitList()
#10 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#11 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(67): GuzzleHttp\Promise\Promise->wait()
#12 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Promise\Coroutine->GuzzleHttp\Promise\{closure}(true)
#13 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#14 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#15 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(103): GuzzleHttp\Promise\Promise->wait(true)
#16 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(77): GuzzleHttp\Promise\Coroutine->wait()
#17 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(153): GuzzleHttp\Command\ServiceClient->execute(Object(GuzzleHttp\Command\Command))
#18 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(269): GuzzleHttp\Command\ServiceClient->__call(‘PutObject’, Array)
#19 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(321): Qcloud\Cos\Client->__call(‘putObject’, Array)
#20 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(36): Qcloud\Cos\Client->upload(‘chonwuleyuan-12…’, ‘e871b9dcd3356f7…’, Object(GuzzleHttp\Psr7\Stream))
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘e871b9dcd3356f7…’)
#22 {main}” width=”1227″ height=”47″>

Efficacy 作用效果

Imepitoin was initially developed as a new AED for humans, but, the more favourable pharmacokinetic profile of imepitoin in dogs versus humans led to the decision to develop imepitoin for the treatment of canine idiopathic epilepsy [102]. Based on randomized controlled trials that demonstrated antiepileptic efficacy, high tolerability and safety in epileptic dogs, the drug was approved in 2013 for this indication in Europe [64, 98, 122]. It has been recommended to use imepitoin in dogs with idiopathic epilepsy experiencing recurrent single generalized epileptic seizures, however, its efficacy has not yet been demonstrated in dogs with cluster seizures or status epilepticus [30]. In a recent randomized controlled study [122], the efficacy of imepitoin was compared with PB in 226 client-owned dogs. The administration of imepitoin twice daily in incremental doses of 10, 20 or 30 mg/kg demonstrated that the majority of dogs with idiopathic epilepsy were managed successfully with imepitoin without significant difference to the efficacy of PB. The frequency of adverse events (e.g. sedation, polydipsia, polyphagia) was significantly higher in the PB group [122]. In a study by Rieck et al. (2006) [98], dogs with chronic epilepsy not responding to PB or primidone received imepitoin (in its initial formulation) or KBr as adjunct AED and the seizure frequency improved to a similar degree in both groups. According to Charalambous et al. (2014) [17], there is good evidence for recommending the use of imepitoin as monotherapy in dogs with recurrent single generalized epileptic seizures, but insufficient evidence for use as adjunct AED. At present, scientific data and evidence-based guidelines on which AED can best be combined with imepitoin are lacking, and further research is needed. Nevertheless, at this moment, the authors recommend the use of PB as adjunct AED in dogs receiving the maximum dose of imepitoin and experiencing poor seizure control. According to the authors, in case of combined therapy with imepitoin and PB, it is advised to slowly wean off imepitoin over several months if seizure control appears successful on PB and/or to reduce the dose of imepitoin if adverse effects (e.g. sedation) occur (Fig. 2).

伊匹妥因 Imepitoin 最初是人类的一种新型抗癫痫药物,但是,与人类相比,伊匹妥因在犬体内的药代动力学特征更可观,因此开始尝试用于治疗犬特发性癫痫[102]。基于随机对照试验,该药物在癫痫犬中具有抗癫痫疗效、高耐受性和安全性,于2013年在欧洲获批准用于此适应症[64,98,122]。已有研究建议对复发性单次全身性癫痫性抽搐发作的特发性癫痫犬使用伊匹妥因,但其对丛集性抽搐发作或癫痫持续状态犬的疗效尚未得到证实[30]。在最近的一项随机对照研究[122]中,对226例客户拥有的犬进行了伊匹妥因与苯巴比妥的疗效比较。每日两次以10、20或30 mg/kg的增量剂量给药,结果表明,大多数特发性癫痫犬均能成功地使用伊匹妥因治疗,对苯巴比妥的疗效无显著影响。不良反应(如镇静、多饮、食欲亢进)的发生频率在苯巴比妥(PB)组明显更高[122]。在Rieck等人(2006年)[98]的研究中,对苯巴比妥或扑米酮(primidone)无反应的慢性癫痫犬接受伊匹妥因(初始制剂)或溴化钾作为辅助抗癫痫药物,两组抽出发作频率均有相似程度的改善。根据 Charalambous等人(2014年)[17]的研究,有充分的证据建议对复发性单次全身性癫痫性抽搐发作的犬使用伊匹妥因作为单药治疗,但没有足够的证据支持将其作为辅助性抗癫痫药物。目前,抗癫痫药物与伊匹妥因联合应用的最佳方法缺乏科学数据和循证指南,有待进一步研究。然而,目前,作者建议在接受最大剂量伊匹妥因且抽搐发作控制不佳的犬中使用苯巴比妥(PB)作为辅助抗癫痫药物。根据作者的说法,在伊匹妥因和苯巴比妥(PB)联合治疗的情况下,如果苯巴比妥(PB)治疗成功地控制了抽搐发作,建议在几个月内慢慢减量停用伊匹妥因,如果出现不良反应(如镇静),建议减少伊匹妥因的剂量(图2)。

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GuzzleHttp\Exception\RequestException: cURL error 0: The connection unexpectedly failed without providing an error. The request would have been retried, but attempting to rewind the request body failed. Exception: RuntimeException: Stream is not seekable in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\psr7\src\Stream.php:204
Stack trace:
#0 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\psr7\src\Stream.php(193): GuzzleHttp\Psr7\Stream->seek(0)
#1 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(517): GuzzleHttp\Psr7\Stream->rewind()
#2 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(152): GuzzleHttp\Handler\CurlFactory::retryFailedRewind(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Array)
#3 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(105): GuzzleHttp\Handler\CurlFactory::finishError(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#4 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(201): GuzzleHttp\Handler\CurlFactory::finish(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#5 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(130): GuzzleHttp\Handler\CurlMultiHandler->processMessages()
#6 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(145): GuzzleHttp\Handler\CurlMultiHandler->tick()
#7 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Handler\CurlMultiHandler->execute(true)
#8 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#9 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(269): GuzzleHttp\Promise\Promise->waitIfPending()
#10 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(226): GuzzleHttp\Promise\Promise->invokeWaitList()
#11 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#12 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(67): GuzzleHttp\Promise\Promise->wait()
#13 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Promise\Coroutine->GuzzleHttp\Promise\{closure}(true)
#14 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#15 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#16 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(103): GuzzleHttp\Promise\Promise->wait(true)
#17 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(77): GuzzleHttp\Promise\Coroutine->wait()
#18 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(153): GuzzleHttp\Command\ServiceClient->execute(Object(GuzzleHttp\Command\Command))
#19 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(269): GuzzleHttp\Command\ServiceClient->__call(‘PutObject’, Array)
#20 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(321): Qcloud\Cos\Client->__call(‘putObject’, Array)
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(36): Qcloud\Cos\Client->upload(‘chonwuleyuan-12…’, ‘321a7ed40099da6…’, Object(GuzzleHttp\Psr7\Stream))
#22 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘321a7ed40099da6…’)
#23 {main} (see https://curl.haxx.se/libcurl/c/libcurl-errors.html) in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php:201
Stack trace:
#0 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(524): GuzzleHttp\Handler\CurlFactory::createRejection(Object(GuzzleHttp\Handler\EasyHandle), Array)
#1 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(152): GuzzleHttp\Handler\CurlFactory::retryFailedRewind(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Array)
#2 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(105): GuzzleHttp\Handler\CurlFactory::finishError(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#3 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(201): GuzzleHttp\Handler\CurlFactory::finish(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#4 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(130): GuzzleHttp\Handler\CurlMultiHandler->processMessages()
#5 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(145): GuzzleHttp\Handler\CurlMultiHandler->tick()
#6 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Handler\CurlMultiHandler->execute(true)
#7 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#8 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(269): GuzzleHttp\Promise\Promise->waitIfPending()
#9 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(226): GuzzleHttp\Promise\Promise->invokeWaitList()
#10 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#11 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(67): GuzzleHttp\Promise\Promise->wait()
#12 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Promise\Coroutine->GuzzleHttp\Promise\{closure}(true)
#13 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#14 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#15 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(103): GuzzleHttp\Promise\Promise->wait(true)
#16 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(77): GuzzleHttp\Promise\Coroutine->wait()
#17 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(153): GuzzleHttp\Command\ServiceClient->execute(Object(GuzzleHttp\Command\Command))
#18 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(269): GuzzleHttp\Command\ServiceClient->__call(‘PutObject’, Array)
#19 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(321): Qcloud\Cos\Client->__call(‘putObject’, Array)
#20 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(36): Qcloud\Cos\Client->upload(‘chonwuleyuan-12…’, ‘321a7ed40099da6…’, Object(GuzzleHttp\Psr7\Stream))
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘321a7ed40099da6…’)
#22 {main}” width=”1227″ height=”47″>

Pharmacokinetics

药代动力学

Following oral administration of imepitoin at a dose of 30 mg/kg in healthy Beagle dogs, high plasma levels were observed within 30 min, but maximal plasma levels were only reached after 2-3h following a prolonged absorption time [101]. The elimination half-life was found to be short; approximately 1.5 to 2h. However, in another study in Beagle dogs, a longer half-life (~6 h) was found after higher doses of imepitoin, and accumulation of plasma levels was seen during chronic BID treatment [64]. Also, it has to be considered that Beagle dogs eliminate AEDs more rapidly than other dog strains [122]. Despite the short half-life in healthy Beagle dogs, this pharmacokinetic profile is reported as adequate to maintain therapeutically active concentrations with twice daily dosing in dogs [64, 122]. Imepitoin is extensively metabolized in the liver prior to elimination. In dogs, imepitoin is mainly excreted via the faecal route rather than the urinary route. Neither reduced kidney function nor impaired liver function is likely to greatly influence the pharmacokinetics of imepitoin [122].

健康的比格犬口服30mg/kg剂量的伊匹妥因后,在30分钟内观察到高血药浓度,但在延迟吸收时间2-3h后才达到最高血浆水平[101]。而且消除半衰期很短;约1.5到2小时。然而,在另一项对比格犬的研究中,更高剂量的伊匹妥因的半衰期更长(~6小时),并且在长期每日两次(BID)治疗期间可观察到血药浓度的积累[64]。此外,必须考虑到比格犬比其他犬种能更快地消除抗癫痫药物[122]。尽管在健康的比格犬中半衰期较短,但据报道,这种药代动力学特征足以在犬中维持每日两次的有效治疗浓度[64,122]。在消除之前,伊匹妥因在肝脏中被广泛代谢。在犬体内伊匹妥因主要通过粪便而不是尿液排出体外。无论是肾功能降低还是肝功能受损都不太可能对伊匹妥因的药代动力学产生很大影响[122]。

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GuzzleHttp\Exception\RequestException: cURL error 0: The connection unexpectedly failed without providing an error. The request would have been retried, but attempting to rewind the request body failed. Exception: RuntimeException: Stream is not seekable in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\psr7\src\Stream.php:204
Stack trace:
#0 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\psr7\src\Stream.php(193): GuzzleHttp\Psr7\Stream->seek(0)
#1 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(517): GuzzleHttp\Psr7\Stream->rewind()
#2 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(152): GuzzleHttp\Handler\CurlFactory::retryFailedRewind(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Array)
#3 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(105): GuzzleHttp\Handler\CurlFactory::finishError(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#4 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(201): GuzzleHttp\Handler\CurlFactory::finish(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#5 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(130): GuzzleHttp\Handler\CurlMultiHandler->processMessages()
#6 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(145): GuzzleHttp\Handler\CurlMultiHandler->tick()
#7 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Handler\CurlMultiHandler->execute(true)
#8 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#9 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(269): GuzzleHttp\Promise\Promise->waitIfPending()
#10 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(226): GuzzleHttp\Promise\Promise->invokeWaitList()
#11 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#12 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(67): GuzzleHttp\Promise\Promise->wait()
#13 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Promise\Coroutine->GuzzleHttp\Promise\{closure}(true)
#14 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#15 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#16 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(103): GuzzleHttp\Promise\Promise->wait(true)
#17 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(77): GuzzleHttp\Promise\Coroutine->wait()
#18 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(153): GuzzleHttp\Command\ServiceClient->execute(Object(GuzzleHttp\Command\Command))
#19 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(269): GuzzleHttp\Command\ServiceClient->__call(‘PutObject’, Array)
#20 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(321): Qcloud\Cos\Client->__call(‘putObject’, Array)
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(36): Qcloud\Cos\Client->upload(‘chonwuleyuan-12…’, ‘c2307e58d9bd065…’, Object(GuzzleHttp\Psr7\Stream))
#22 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘c2307e58d9bd065…’)
#23 {main} (see https://curl.haxx.se/libcurl/c/libcurl-errors.html) in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php:201
Stack trace:
#0 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(524): GuzzleHttp\Handler\CurlFactory::createRejection(Object(GuzzleHttp\Handler\EasyHandle), Array)
#1 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(152): GuzzleHttp\Handler\CurlFactory::retryFailedRewind(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Array)
#2 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(105): GuzzleHttp\Handler\CurlFactory::finishError(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#3 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(201): GuzzleHttp\Handler\CurlFactory::finish(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#4 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(130): GuzzleHttp\Handler\CurlMultiHandler->processMessages()
#5 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(145): GuzzleHttp\Handler\CurlMultiHandler->tick()
#6 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Handler\CurlMultiHandler->execute(true)
#7 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#8 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(269): GuzzleHttp\Promise\Promise->waitIfPending()
#9 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(226): GuzzleHttp\Promise\Promise->invokeWaitList()
#10 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#11 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(67): GuzzleHttp\Promise\Promise->wait()
#12 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Promise\Coroutine->GuzzleHttp\Promise\{closure}(true)
#13 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#14 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#15 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(103): GuzzleHttp\Promise\Promise->wait(true)
#16 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(77): GuzzleHttp\Promise\Coroutine->wait()
#17 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(153): GuzzleHttp\Command\ServiceClient->execute(Object(GuzzleHttp\Command\Command))
#18 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(269): GuzzleHttp\Command\ServiceClient->__call(‘PutObject’, Array)
#19 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(321): Qcloud\Cos\Client->__call(‘putObject’, Array)
#20 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(36): Qcloud\Cos\Client->upload(‘chonwuleyuan-12…’, ‘c2307e58d9bd065…’, Object(GuzzleHttp\Psr7\Stream))
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘c2307e58d9bd065…’)
#22 {main}” width=”1227″ height=”47″>

Pharmacokinetic interactions and adverse reactions

药代动力学相互作用和副作用

There is no information on pharmacokinetic interactions between imepitoin and other medications. Although, imepitoin is a low affinity partial agonist for the benzodiazepine binding site of the GABAA receptor it has not prevented the pharmacological activity of full benzodiazepine agonists such as diazepam in the clinical setting (e.g. in dogs with status epilepticus) [122]. Consequently, because the affinity of diazepam for the GABAA receptor is much higher than imepitoin, care should be taken in the emergency setting [122]. Therefore, dogs with idiopathic epilepsy treated with imepitoin and presented in status epilepticus might require, in addition to diazepam, an additional AED parenterally (e.g. PB, levetiracetam).

目前还没有关于伊匹妥因和其他药物之间的药代动力学相互作用的信息。尽管依匹妥因是GABAA受体苯二氮卓结合位点的低亲和力部分激动剂,但在临床环境中,它并没有阻止全苯二氮卓激动剂(如地西泮)的药理活性(例如,在癫痫持续状态的犬中)[122]。因此,由于地西泮对GABAA受体的亲和力远高于伊匹妥因,因此在紧急情况下应注意使用[122]。因此,接受伊匹妥因治疗并呈现癫痫持续状态的特发性癫痫犬,除了地西泮外,可能还需要额外的抗癫痫药物(如苯巴比妥、左乙拉西坦levetiracetam)。

<img data-src="
Warning: curl_setopt_array(): Unable to create temporary file. in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php on line 59
GuzzleHttp\Exception\RequestException: cURL error 0: The connection unexpectedly failed without providing an error. The request would have been retried, but attempting to rewind the request body failed. Exception: RuntimeException: Stream is not seekable in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\psr7\src\Stream.php:204
Stack trace:
#0 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\psr7\src\Stream.php(193): GuzzleHttp\Psr7\Stream->seek(0)
#1 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(517): GuzzleHttp\Psr7\Stream->rewind()
#2 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(152): GuzzleHttp\Handler\CurlFactory::retryFailedRewind(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Array)
#3 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(105): GuzzleHttp\Handler\CurlFactory::finishError(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#4 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(201): GuzzleHttp\Handler\CurlFactory::finish(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#5 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(130): GuzzleHttp\Handler\CurlMultiHandler->processMessages()
#6 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(145): GuzzleHttp\Handler\CurlMultiHandler->tick()
#7 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Handler\CurlMultiHandler->execute(true)
#8 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#9 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(269): GuzzleHttp\Promise\Promise->waitIfPending()
#10 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(226): GuzzleHttp\Promise\Promise->invokeWaitList()
#11 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#12 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(67): GuzzleHttp\Promise\Promise->wait()
#13 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Promise\Coroutine->GuzzleHttp\Promise\{closure}(true)
#14 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#15 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#16 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(103): GuzzleHttp\Promise\Promise->wait(true)
#17 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(77): GuzzleHttp\Promise\Coroutine->wait()
#18 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(153): GuzzleHttp\Command\ServiceClient->execute(Object(GuzzleHttp\Command\Command))
#19 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(269): GuzzleHttp\Command\ServiceClient->__call(‘PutObject’, Array)
#20 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(321): Qcloud\Cos\Client->__call(‘putObject’, Array)
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(36): Qcloud\Cos\Client->upload(‘chonwuleyuan-12…’, ‘a9ac9ee384d616e…’, Object(GuzzleHttp\Psr7\Stream))
#22 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘a9ac9ee384d616e…’)
#23 {main} (see https://curl.haxx.se/libcurl/c/libcurl-errors.html) in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php:201
Stack trace:
#0 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(524): GuzzleHttp\Handler\CurlFactory::createRejection(Object(GuzzleHttp\Handler\EasyHandle), Array)
#1 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(152): GuzzleHttp\Handler\CurlFactory::retryFailedRewind(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Array)
#2 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(105): GuzzleHttp\Handler\CurlFactory::finishError(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#3 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(201): GuzzleHttp\Handler\CurlFactory::finish(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#4 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(130): GuzzleHttp\Handler\CurlMultiHandler->processMessages()
#5 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(145): GuzzleHttp\Handler\CurlMultiHandler->tick()
#6 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Handler\CurlMultiHandler->execute(true)
#7 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#8 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(269): GuzzleHttp\Promise\Promise->waitIfPending()
#9 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(226): GuzzleHttp\Promise\Promise->invokeWaitList()
#10 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#11 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(67): GuzzleHttp\Promise\Promise->wait()
#12 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Promise\Coroutine->GuzzleHttp\Promise\{closure}(true)
#13 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#14 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#15 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(103): GuzzleHttp\Promise\Promise->wait(true)
#16 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(77): GuzzleHttp\Promise\Coroutine->wait()
#17 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(153): GuzzleHttp\Command\ServiceClient->execute(Object(GuzzleHttp\Command\Command))
#18 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(269): GuzzleHttp\Command\ServiceClient->__call(‘PutObject’, Array)
#19 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(321): Qcloud\Cos\Client->__call(‘putObject’, Array)
#20 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(36): Qcloud\Cos\Client->upload(‘chonwuleyuan-12…’, ‘a9ac9ee384d616e…’, Object(GuzzleHttp\Psr7\Stream))
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘a9ac9ee384d616e…’)
#22 {main}” width=”1227″ height=”47″>

Mild and most commonly transient adverse reactions (Table 1) have been reported in dogs administered 10-30 mg/kg BID of imepitoin in its initial formulation; polyphagia at the beginning of the treatment, hyperactivity, polyuria, polydipsia, somnolence, hypersalivation, emesis, ataxia, lethargy, diarrhoea, prolapsed nictitating membranes, decreased vision and sensitivity to sound [64, 98].

据报道,在初始剂量给予10 – 30 mg/kg BID的伊匹妥因的犬中,出现了轻微和最常见的暂时性不良反应(表1);治疗初期多食、过度活跃、多尿、多饮、冷漠、过度流涎、呕吐、共济失调、嗜睡、腹泻、第三眼睑脱出、视力下降和对声音的敏感[64,98]

<img data-src="
Warning: curl_setopt_array(): Unable to create temporary file. in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php on line 59
GuzzleHttp\Exception\RequestException: cURL error 0: The connection unexpectedly failed without providing an error. The request would have been retried, but attempting to rewind the request body failed. Exception: RuntimeException: Stream is not seekable in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\psr7\src\Stream.php:204
Stack trace:
#0 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\psr7\src\Stream.php(193): GuzzleHttp\Psr7\Stream->seek(0)
#1 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(517): GuzzleHttp\Psr7\Stream->rewind()
#2 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(152): GuzzleHttp\Handler\CurlFactory::retryFailedRewind(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Array)
#3 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(105): GuzzleHttp\Handler\CurlFactory::finishError(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#4 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(201): GuzzleHttp\Handler\CurlFactory::finish(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#5 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(130): GuzzleHttp\Handler\CurlMultiHandler->processMessages()
#6 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(145): GuzzleHttp\Handler\CurlMultiHandler->tick()
#7 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Handler\CurlMultiHandler->execute(true)
#8 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#9 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(269): GuzzleHttp\Promise\Promise->waitIfPending()
#10 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(226): GuzzleHttp\Promise\Promise->invokeWaitList()
#11 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#12 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(67): GuzzleHttp\Promise\Promise->wait()
#13 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Promise\Coroutine->GuzzleHttp\Promise\{closure}(true)
#14 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#15 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#16 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(103): GuzzleHttp\Promise\Promise->wait(true)
#17 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(77): GuzzleHttp\Promise\Coroutine->wait()
#18 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(153): GuzzleHttp\Command\ServiceClient->execute(Object(GuzzleHttp\Command\Command))
#19 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(269): GuzzleHttp\Command\ServiceClient->__call(‘PutObject’, Array)
#20 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(321): Qcloud\Cos\Client->__call(‘putObject’, Array)
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(36): Qcloud\Cos\Client->upload(‘chonwuleyuan-12…’, ‘872004802a1a75b…’, Object(GuzzleHttp\Psr7\Stream))
#22 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘872004802a1a75b…’)
#23 {main} (see https://curl.haxx.se/libcurl/c/libcurl-errors.html) in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php:201
Stack trace:
#0 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(524): GuzzleHttp\Handler\CurlFactory::createRejection(Object(GuzzleHttp\Handler\EasyHandle), Array)
#1 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(152): GuzzleHttp\Handler\CurlFactory::retryFailedRewind(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Array)
#2 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(105): GuzzleHttp\Handler\CurlFactory::finishError(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#3 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(201): GuzzleHttp\Handler\CurlFactory::finish(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#4 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(130): GuzzleHttp\Handler\CurlMultiHandler->processMessages()
#5 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(145): GuzzleHttp\Handler\CurlMultiHandler->tick()
#6 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Handler\CurlMultiHandler->execute(true)
#7 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#8 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(269): GuzzleHttp\Promise\Promise->waitIfPending()
#9 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(226): GuzzleHttp\Promise\Promise->invokeWaitList()
#10 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#11 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(67): GuzzleHttp\Promise\Promise->wait()
#12 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Promise\Coroutine->GuzzleHttp\Promise\{closure}(true)
#13 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#14 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#15 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(103): GuzzleHttp\Promise\Promise->wait(true)
#16 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(77): GuzzleHttp\Promise\Coroutine->wait()
#17 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(153): GuzzleHttp\Command\ServiceClient->execute(Object(GuzzleHttp\Command\Command))
#18 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(269): GuzzleHttp\Command\ServiceClient->__call(‘PutObject’, Array)
#19 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(321): Qcloud\Cos\Client->__call(‘putObject’, Array)
#20 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(36): Qcloud\Cos\Client->upload(‘chonwuleyuan-12…’, ‘872004802a1a75b…’, Object(GuzzleHttp\Psr7\Stream))
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘872004802a1a75b…’)
#22 {main}” width=”1227″ height=”47″>

As part of the development of imepitoin for the treatment of canine epilepsy, a target animal safety study in dogs was conducted [96]. Under laboratory conditions, healthy Beagle dogs were exposed to high doses (up to 150 mg/kg q12h) of imepitoin for 6 months. Clinical signs of toxicity were mild and infrequent and they were mostly CNS (depression, transient ataxia) or gastrointestinal system (vomiting, body weight loss, salivation) related. These clinical signs were not life-threatening and generally resolved within 24h if symptomatic treatment was given. These data indicate that imepitoin is a safe AED and is well tolerated up to high doses in dogs treated twice daily [96]. However, the safety of imepitoin has not been evaluated in dogs weighing less than 5 kg or in dogs with safety concerns such as renal, liver cardiac, gastrointestinal or other disease. No idiosyncratic reactions have been demonstrated so far. The routinely measured liver enzymes’ activity do not appear to be induced by imepitoin [96]. Compared with the traditional benzodiazepines, such as diazepam, which acts as full agonists at the benzodiazepine site of the GABAA receptor, partial agonists such as imepitoin show less sedative adverse effects and are not associated with tolerance and dependence during long-term administration in animal models [122]. Also in epileptic dogs, tolerance did not develop and no withdrawal signs were observed after treatment discontinuation [64].

作为研究伊匹妥因治疗犬癫痫的发展一部分,在犬中进行了靶向动物安全性研究[96]。在实验室条件下,健康的比格犬暴露于高剂量(高达150mg /kg q12h)的伊匹妥因6个月。临床症状轻微且少见,主要与中枢神经系统(沉郁、一过性共济失调)或胃肠道系统(呕吐、体重减轻、流涎)有关。这些临床症状不危及生命,如果给予对症治疗,一般在24小时内消失。这些数据表明,伊匹妥因是一种安全的抗癫痫药,对于每天给药两次的犬来说,即使是大剂量,也具有良好的耐受性[96]。然而,尚未对于体重小于5公斤,或有肾脏、肝脏、心脏、胃肠道或其他疾病等安全问题的犬进行伊匹妥因的安全性评估。目前还没有发现有特质性反应(idiosyncratic reactions)。常规测量的肝酶活性似乎并不是由伊匹妥因导致的[96]。与传统的苯二氮卓类药物,如地西泮,在GABAA受体的苯二氮卓位点的完全激动剂相比,部分激动剂如伊匹妥因,在动物模型中表现出更小的镇静副作用,并且在长期给药过程中不存在耐受性和依赖性[122]。同样在癫痫犬中,停药后未产生耐受性,也未观察到戒断症状[64]。

<img data-src="
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GuzzleHttp\Exception\RequestException: cURL error 0: The connection unexpectedly failed without providing an error. The request would have been retried, but attempting to rewind the request body failed. Exception: RuntimeException: Stream is not seekable in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\psr7\src\Stream.php:204
Stack trace:
#0 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\psr7\src\Stream.php(193): GuzzleHttp\Psr7\Stream->seek(0)
#1 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(517): GuzzleHttp\Psr7\Stream->rewind()
#2 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(152): GuzzleHttp\Handler\CurlFactory::retryFailedRewind(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Array)
#3 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(105): GuzzleHttp\Handler\CurlFactory::finishError(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#4 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(201): GuzzleHttp\Handler\CurlFactory::finish(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#5 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(130): GuzzleHttp\Handler\CurlMultiHandler->processMessages()
#6 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(145): GuzzleHttp\Handler\CurlMultiHandler->tick()
#7 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Handler\CurlMultiHandler->execute(true)
#8 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#9 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(269): GuzzleHttp\Promise\Promise->waitIfPending()
#10 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(226): GuzzleHttp\Promise\Promise->invokeWaitList()
#11 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#12 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(67): GuzzleHttp\Promise\Promise->wait()
#13 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Promise\Coroutine->GuzzleHttp\Promise\{closure}(true)
#14 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#15 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#16 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(103): GuzzleHttp\Promise\Promise->wait(true)
#17 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(77): GuzzleHttp\Promise\Coroutine->wait()
#18 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(153): GuzzleHttp\Command\ServiceClient->execute(Object(GuzzleHttp\Command\Command))
#19 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(269): GuzzleHttp\Command\ServiceClient->__call(‘PutObject’, Array)
#20 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(321): Qcloud\Cos\Client->__call(‘putObject’, Array)
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(36): Qcloud\Cos\Client->upload(‘chonwuleyuan-12…’, ‘709eb418de6c331…’, Object(GuzzleHttp\Psr7\Stream))
#22 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘709eb418de6c331…’)
#23 {main} (see https://curl.haxx.se/libcurl/c/libcurl-errors.html) in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php:201
Stack trace:
#0 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(524): GuzzleHttp\Handler\CurlFactory::createRejection(Object(GuzzleHttp\Handler\EasyHandle), Array)
#1 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(152): GuzzleHttp\Handler\CurlFactory::retryFailedRewind(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Array)
#2 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(105): GuzzleHttp\Handler\CurlFactory::finishError(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#3 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(201): GuzzleHttp\Handler\CurlFactory::finish(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#4 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(130): GuzzleHttp\Handler\CurlMultiHandler->processMessages()
#5 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(145): GuzzleHttp\Handler\CurlMultiHandler->tick()
#6 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Handler\CurlMultiHandler->execute(true)
#7 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#8 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(269): GuzzleHttp\Promise\Promise->waitIfPending()
#9 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(226): GuzzleHttp\Promise\Promise->invokeWaitList()
#10 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#11 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(67): GuzzleHttp\Promise\Promise->wait()
#12 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Promise\Coroutine->GuzzleHttp\Promise\{closure}(true)
#13 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#14 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#15 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(103): GuzzleHttp\Promise\Promise->wait(true)
#16 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(77): GuzzleHttp\Promise\Coroutine->wait()
#17 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(153): GuzzleHttp\Command\ServiceClient->execute(Object(GuzzleHttp\Command\Command))
#18 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(269): GuzzleHttp\Command\ServiceClient->__call(‘PutObject’, Array)
#19 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(321): Qcloud\Cos\Client->__call(‘putObject’, Array)
#20 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(36): Qcloud\Cos\Client->upload(‘chonwuleyuan-12…’, ‘709eb418de6c331…’, Object(GuzzleHttp\Psr7\Stream))
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘709eb418de6c331…’)
#22 {main}” width=”1227″ height=”47″>

Dose and monitoring (Fig. 2)

剂量与监测(图2)

The oral dose range of imepitoin is 10-30 mg/kg BID. The recommended oral starting dose of imepitoin is 10-20 mg/kg BID. If seizure control is not satisfactory after at least 1 week of treatment at this dose and the medication is well tolerated, the dose can be increased up to a maximum of 30 mg/kg BID. Reference range of plasma or serum imepitoin concentrations is unknown and there are no therapeutic monitoring recommendations for imepitoin from the manufacturer. Pharmacokinetic studies in dogs suggest variability in plasma imepitoin concentrations among individuals and sampling times. However, no correlation between plasma imepitoin concentration and seizure frequency reduction was identified [64] therefore and because of its wide therapeutic index, serum imepitoin monitoring is not needed. The authors recommend a complete blood cell count and biochemical profile before starting imepitoin treatment and periodically every 6 months during treatment. If the dog is in remission or has no seizures, a periodical control every 12 months is advised.

伊匹妥因的口服剂量范围为10 ~ 30 mg/kg BID。口服伊匹妥因的推荐起始剂量为10 ~ 20mg /kg BID。如果此剂量用药至少1周后抽搐发作控制不充分,且药物耐受性良好,则可将剂量增加至最高30 mg/kg BID。血浆或血清伊匹妥因浓度的参考范围尚不清楚,厂商也没有对伊匹妥因的治疗监测建议。犬的药代动力学研究表明,个体之间和采样时间之间的伊匹妥因血浆浓度存在可变差异。然而,没有发现伊匹妥因血浆浓度与抽搐发作频率减少之间的相关性[64],因此,由于其宽泛的有效治疗指数,依匹妥因血清监测是不必要的。作者建议在开始使用依妥匹因治疗前进行全血细胞计数和生化检查,并在治疗期间每6个月定期检查一次。如果犬的症状缓解或没有抽搐发作,建议每12个月检查一次。

<img data-src="
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GuzzleHttp\Exception\RequestException: cURL error 0: The connection unexpectedly failed without providing an error. The request would have been retried, but attempting to rewind the request body failed. Exception: RuntimeException: Stream is not seekable in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\psr7\src\Stream.php:204
Stack trace:
#0 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\psr7\src\Stream.php(193): GuzzleHttp\Psr7\Stream->seek(0)
#1 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(517): GuzzleHttp\Psr7\Stream->rewind()
#2 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(152): GuzzleHttp\Handler\CurlFactory::retryFailedRewind(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Array)
#3 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(105): GuzzleHttp\Handler\CurlFactory::finishError(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#4 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(201): GuzzleHttp\Handler\CurlFactory::finish(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#5 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(130): GuzzleHttp\Handler\CurlMultiHandler->processMessages()
#6 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(145): GuzzleHttp\Handler\CurlMultiHandler->tick()
#7 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Handler\CurlMultiHandler->execute(true)
#8 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#9 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(269): GuzzleHttp\Promise\Promise->waitIfPending()
#10 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(226): GuzzleHttp\Promise\Promise->invokeWaitList()
#11 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#12 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(67): GuzzleHttp\Promise\Promise->wait()
#13 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Promise\Coroutine->GuzzleHttp\Promise\{closure}(true)
#14 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#15 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#16 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(103): GuzzleHttp\Promise\Promise->wait(true)
#17 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(77): GuzzleHttp\Promise\Coroutine->wait()
#18 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(153): GuzzleHttp\Command\ServiceClient->execute(Object(GuzzleHttp\Command\Command))
#19 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(269): GuzzleHttp\Command\ServiceClient->__call(‘PutObject’, Array)
#20 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(321): Qcloud\Cos\Client->__call(‘putObject’, Array)
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(36): Qcloud\Cos\Client->upload(‘chonwuleyuan-12…’, ‘22111c8bb6b0718…’, Object(GuzzleHttp\Psr7\Stream))
#22 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘22111c8bb6b0718…’)
#23 {main} (see https://curl.haxx.se/libcurl/c/libcurl-errors.html) in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php:201
Stack trace:
#0 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(524): GuzzleHttp\Handler\CurlFactory::createRejection(Object(GuzzleHttp\Handler\EasyHandle), Array)
#1 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(152): GuzzleHttp\Handler\CurlFactory::retryFailedRewind(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Array)
#2 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(105): GuzzleHttp\Handler\CurlFactory::finishError(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#3 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(201): GuzzleHttp\Handler\CurlFactory::finish(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#4 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(130): GuzzleHttp\Handler\CurlMultiHandler->processMessages()
#5 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(145): GuzzleHttp\Handler\CurlMultiHandler->tick()
#6 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Handler\CurlMultiHandler->execute(true)
#7 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#8 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(269): GuzzleHttp\Promise\Promise->waitIfPending()
#9 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(226): GuzzleHttp\Promise\Promise->invokeWaitList()
#10 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#11 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(67): GuzzleHttp\Promise\Promise->wait()
#12 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Promise\Coroutine->GuzzleHttp\Promise\{closure}(true)
#13 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#14 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#15 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(103): GuzzleHttp\Promise\Promise->wait(true)
#16 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(77): GuzzleHttp\Promise\Coroutine->wait()
#17 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(153): GuzzleHttp\Command\ServiceClient->execute(Object(GuzzleHttp\Command\Command))
#18 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(269): GuzzleHttp\Command\ServiceClient->__call(‘PutObject’, Array)
#19 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(321): Qcloud\Cos\Client->__call(‘putObject’, Array)
#20 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(36): Qcloud\Cos\Client->upload(‘chonwuleyuan-12…’, ‘22111c8bb6b0718…’, Object(GuzzleHttp\Psr7\Stream))
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘22111c8bb6b0718…’)
#22 {main}” width=”1227″ height=”47″>
<img data-src="
Warning: curl_setopt_array(): Unable to create temporary file. in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php on line 59
GuzzleHttp\Exception\RequestException: cURL error 0: The connection unexpectedly failed without providing an error. The request would have been retried, but attempting to rewind the request body failed. Exception: RuntimeException: Stream is not seekable in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\psr7\src\Stream.php:204
Stack trace:
#0 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\psr7\src\Stream.php(193): GuzzleHttp\Psr7\Stream->seek(0)
#1 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(517): GuzzleHttp\Psr7\Stream->rewind()
#2 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(152): GuzzleHttp\Handler\CurlFactory::retryFailedRewind(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Array)
#3 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(105): GuzzleHttp\Handler\CurlFactory::finishError(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#4 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(201): GuzzleHttp\Handler\CurlFactory::finish(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#5 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(130): GuzzleHttp\Handler\CurlMultiHandler->processMessages()
#6 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(145): GuzzleHttp\Handler\CurlMultiHandler->tick()
#7 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Handler\CurlMultiHandler->execute(true)
#8 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#9 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(269): GuzzleHttp\Promise\Promise->waitIfPending()
#10 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(226): GuzzleHttp\Promise\Promise->invokeWaitList()
#11 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#12 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(67): GuzzleHttp\Promise\Promise->wait()
#13 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Promise\Coroutine->GuzzleHttp\Promise\{closure}(true)
#14 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#15 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#16 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(103): GuzzleHttp\Promise\Promise->wait(true)
#17 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(77): GuzzleHttp\Promise\Coroutine->wait()
#18 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(153): GuzzleHttp\Command\ServiceClient->execute(Object(GuzzleHttp\Command\Command))
#19 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(269): GuzzleHttp\Command\ServiceClient->__call(‘PutObject’, Array)
#20 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(321): Qcloud\Cos\Client->__call(‘putObject’, Array)
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(36): Qcloud\Cos\Client->upload(‘chonwuleyuan-12…’, ‘236f05fd5042d4e…’, Object(GuzzleHttp\Psr7\Stream))
#22 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘236f05fd5042d4e…’)
#23 {main} (see https://curl.haxx.se/libcurl/c/libcurl-errors.html) in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php:201
Stack trace:
#0 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(524): GuzzleHttp\Handler\CurlFactory::createRejection(Object(GuzzleHttp\Handler\EasyHandle), Array)
#1 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(152): GuzzleHttp\Handler\CurlFactory::retryFailedRewind(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Array)
#2 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(105): GuzzleHttp\Handler\CurlFactory::finishError(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#3 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(201): GuzzleHttp\Handler\CurlFactory::finish(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#4 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(130): GuzzleHttp\Handler\CurlMultiHandler->processMessages()
#5 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(145): GuzzleHttp\Handler\CurlMultiHandler->tick()
#6 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Handler\CurlMultiHandler->execute(true)
#7 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#8 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(269): GuzzleHttp\Promise\Promise->waitIfPending()
#9 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(226): GuzzleHttp\Promise\Promise->invokeWaitList()
#10 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#11 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(67): GuzzleHttp\Promise\Promise->wait()
#12 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Promise\Coroutine->GuzzleHttp\Promise\{closure}(true)
#13 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#14 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#15 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(103): GuzzleHttp\Promise\Promise->wait(true)
#16 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(77): GuzzleHttp\Promise\Coroutine->wait()
#17 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(153): GuzzleHttp\Command\ServiceClient->execute(Object(GuzzleHttp\Command\Command))
#18 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(269): GuzzleHttp\Command\ServiceClient->__call(‘PutObject’, Array)
#19 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(321): Qcloud\Cos\Client->__call(‘putObject’, Array)
#20 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(36): Qcloud\Cos\Client->upload(‘chonwuleyuan-12…’, ‘236f05fd5042d4e…’, Object(GuzzleHttp\Psr7\Stream))
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘236f05fd5042d4e…’)
#22 {main}” width=”850″ height=”634″>

Fig. 2 Imepitoin treatment flow diagram for decision making during seizure management in an otherwise healthy dog. The authors advise to start with imepitoin in dogs with idiopathic epilepsy experiencing recurrent single generalised epileptic seizures. *Criteria for (in)adequate seizure control with regard to efficacy and tolerability (see Consensus proposal: Outcome of therapeutic interventions in canine and feline epilepsy [94]).

图2 其他方面均健康犬的抽搐发作管理决策过程中使用伊匹妥因治疗的流程图。作者建议对患有特发性癫痫、全身性抽搐反复发作的犬开始使用伊匹妥因。*充分控制抽搐发作的有效性和耐受性标准(见共识提案:犬猫癫痫治疗干预的结果[94])。

<img data-src="
Warning: curl_setopt_array(): Unable to create temporary file. in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php on line 59
GuzzleHttp\Exception\RequestException: cURL error 0: The connection unexpectedly failed without providing an error. The request would have been retried, but attempting to rewind the request body failed. Exception: RuntimeException: Stream is not seekable in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\psr7\src\Stream.php:204
Stack trace:
#0 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\psr7\src\Stream.php(193): GuzzleHttp\Psr7\Stream->seek(0)
#1 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(517): GuzzleHttp\Psr7\Stream->rewind()
#2 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(152): GuzzleHttp\Handler\CurlFactory::retryFailedRewind(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Array)
#3 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(105): GuzzleHttp\Handler\CurlFactory::finishError(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#4 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(201): GuzzleHttp\Handler\CurlFactory::finish(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#5 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(130): GuzzleHttp\Handler\CurlMultiHandler->processMessages()
#6 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(145): GuzzleHttp\Handler\CurlMultiHandler->tick()
#7 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Handler\CurlMultiHandler->execute(true)
#8 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#9 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(269): GuzzleHttp\Promise\Promise->waitIfPending()
#10 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(226): GuzzleHttp\Promise\Promise->invokeWaitList()
#11 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#12 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(67): GuzzleHttp\Promise\Promise->wait()
#13 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Promise\Coroutine->GuzzleHttp\Promise\{closure}(true)
#14 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#15 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#16 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(103): GuzzleHttp\Promise\Promise->wait(true)
#17 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(77): GuzzleHttp\Promise\Coroutine->wait()
#18 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(153): GuzzleHttp\Command\ServiceClient->execute(Object(GuzzleHttp\Command\Command))
#19 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(269): GuzzleHttp\Command\ServiceClient->__call(‘PutObject’, Array)
#20 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(321): Qcloud\Cos\Client->__call(‘putObject’, Array)
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(36): Qcloud\Cos\Client->upload(‘chonwuleyuan-12…’, ‘aeffcef70bde4ee…’, Object(GuzzleHttp\Psr7\Stream))
#22 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘aeffcef70bde4ee…’)
#23 {main} (see https://curl.haxx.se/libcurl/c/libcurl-errors.html) in C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php:201
Stack trace:
#0 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(524): GuzzleHttp\Handler\CurlFactory::createRejection(Object(GuzzleHttp\Handler\EasyHandle), Array)
#1 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(152): GuzzleHttp\Handler\CurlFactory::retryFailedRewind(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Array)
#2 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlFactory.php(105): GuzzleHttp\Handler\CurlFactory::finishError(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#3 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(201): GuzzleHttp\Handler\CurlFactory::finish(Object(GuzzleHttp\Handler\CurlMultiHandler), Object(GuzzleHttp\Handler\EasyHandle), Object(GuzzleHttp\Handler\CurlFactory))
#4 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(130): GuzzleHttp\Handler\CurlMultiHandler->processMessages()
#5 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\guzzle\src\Handler\CurlMultiHandler.php(145): GuzzleHttp\Handler\CurlMultiHandler->tick()
#6 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Handler\CurlMultiHandler->execute(true)
#7 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#8 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(269): GuzzleHttp\Promise\Promise->waitIfPending()
#9 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(226): GuzzleHttp\Promise\Promise->invokeWaitList()
#10 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#11 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(67): GuzzleHttp\Promise\Promise->wait()
#12 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(248): GuzzleHttp\Promise\Coroutine->GuzzleHttp\Promise\{closure}(true)
#13 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(224): GuzzleHttp\Promise\Promise->invokeWaitFn()
#14 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Promise.php(62): GuzzleHttp\Promise\Promise->waitIfPending()
#15 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\promises\src\Coroutine.php(103): GuzzleHttp\Promise\Promise->wait(true)
#16 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(77): GuzzleHttp\Promise\Coroutine->wait()
#17 C:\wwwroot\upimg.chonwuleyuan.com\vendor\guzzlehttp\command\src\ServiceClient.php(153): GuzzleHttp\Command\ServiceClient->execute(Object(GuzzleHttp\Command\Command))
#18 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(269): GuzzleHttp\Command\ServiceClient->__call(‘PutObject’, Array)
#19 C:\wwwroot\upimg.chonwuleyuan.com\src\Client.php(321): Qcloud\Cos\Client->__call(‘putObject’, Array)
#20 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(36): Qcloud\Cos\Client->upload(‘chonwuleyuan-12…’, ‘aeffcef70bde4ee…’, Object(GuzzleHttp\Psr7\Stream))
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘aeffcef70bde4ee…’)
#22 {main}” width=”1227″ height=”47″>

1. Treatment efficacious:

a: Achievement of complete treatment success (i.e. seizure freedom or extension of the interseizure interval to three times the longest pretreatment interseizure interval and for a minimum of three months (ideally

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