国际兽医癫痫工作组共识建议:欧洲犬癫痫的药物治疗丨左乙拉西坦丨翻译节选

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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…’, ‘1a974566cde006e…’, Object(GuzzleHttp\Psr7\Stream))
#22 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘1a974566cde006e…’)
#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…’, ‘1a974566cde006e…’, Object(GuzzleHttp\Psr7\Stream))
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘1a974566cde006e…’)
#22 {main}” width=”625″ height=”351″>

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

左乙拉西坦

So far, three studies evaluated the efficacy of levetiracetam as an adjunct to other AEDs [79, 114, 127]. In all these studies, the majority of the dogs were treated successfully by oral levetiracetam as adjunct AED. The use of oral levetiracetam was evaluated in an open-label study and a response rate of 57 % was reported in dogs with drug resistant epilepsy [127]. In a recent randomized placebo-controlled study by Mu~nana et al. (2012) [79], the use of levetiracetam was evaluated in dogs with drug resistant epilepsy. A significant decrease in seizure frequency was reported compared with baseline, however, no difference was detected in seizure frequency when levetiractam was compared with placebo. However, the divergence in group size and the small sample size (due to the high dropout rate) may have contributed to this result. Nevertheless, a trend towards a decrease in seizure frequency and increase in responder rate during levetiracetam administration compared to placebo warrants further evaluation in a larger scale study. According to the study of Charalambous et al., (2014) [17], there is a fair evidence for recommending the use of levetiracetam as an adjunct AED. Recently, a retrospective study provided further evidence that administering levetiracetam as an adjunct AED is well tolerated, and suppresses epileptic seizures significantly in dogs with idiopathic epilepsy [83]. The authors also confirmed that if seizure frequency increases, an extra AED may be beneficial and they added the possibility of administering levetiracetam as pulse treatment for cluster seizures。

到目前为止,有3项研究评估了左乙拉西坦(levetiracetam)作为其他抗癫痫药物的辅助用药的疗效[79,114,127]。在所有这些研究中,大多数犬通过口服左乙拉西坦作为辅助抗癫痫物而治疗成功。一项开放性研究对口服左乙拉西坦的使用进行了评估,据报道,对耐药癫痫犬的有效率为57%[127]。最近,Mu~nana等人(2012年)[79]进行了一项随机安慰剂对照研究,评估了左乙拉西坦在耐药癫痫犬中的应用。据报道,与基线相比,抽搐发作频率显著降低。但与安慰剂相比,左乙拉西坦组抽搐发作频率方面没有发现差异。然而,群体规模的差异和小样本量(由于高弃除率 dropout rate)可能是导致这一结果的原因。然而,与安慰剂相比,左乙拉西坦治疗期间抽搐发作频率降低和应答率增加的趋势值得在更大规模的研究中进一步评估。Charalambous等(2014年)[17]的研究表明,有充分的证据推荐使用左乙拉西坦作为辅助性抗癫痫药物(adjunct AED)。最近,一项回顾性研究提供了进一步的证据,表明左乙拉西坦作为辅助性抗癫痫药物具有良好的耐受性,可以显著抑制特发性癫痫犬的癫痫性抽搐发作[83]。作者还证实,如果抽搐发作频率升高,增加额外的抗抽搐药物可能是有益的,这增加了使用左乙拉西坦作为丛集性抽搐发作脉冲治疗的可能性。

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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…’, ‘3f94519039c6e5e…’, Object(GuzzleHttp\Psr7\Stream))
#22 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘3f94519039c6e5e…’)
#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…’, ‘3f94519039c6e5e…’, Object(GuzzleHttp\Psr7\Stream))
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘3f94519039c6e5e…’)
#22 {main}” width=”1234″ height=”46″>

Levetiracetam possesses a favourable pharmacokinetic profile in dogs with respect to its use as an add-on AED. It has rapid and complete absorption after oral administration, minimal protein binding, minimal hepatic metabolism and is excreted mainly unchanged via the kidneys. In humans and dogs, renal clearance of levetiracetam is progressively reduced in patients with increasing severity of renal dysfunction [85], thus, dosage reduction should be considered in patients with impaired renal function. As levetiracetam has minimal hepatic metabolism [85], this drug represents a useful therapeutic option in animals with known or suspected hepatic dysfunction. However, its short elimination half-life of 3-6 h necessitates frequent administration. The recommended oral maintenance dose of levetiracetam in dogs is 20 mg/kg TID-QID.

左乙拉西坦在犬身上具有良好的药代动力学特征,可以作为结合性抗癫痫药物(add-on AED)。口服后吸收迅速完全,蛋白质结合少,肝脏代谢少,主要经肾脏排出。在人和犬中,随着肾功能不全程度的加重,左乙拉西坦的肾脏清除率逐渐降低[85],因此,对于肾功能受损的病患,应考虑减少剂量。由于左乙拉西坦的肝脏代谢很少[85],该药物对于已知或疑似肝功能障碍的动物是一种有用的治疗选择。然而,它的消除半衰期很短,只有3 ~ 6小时,因此需要频繁给药。犬的左乙拉西坦的推荐口服维持剂量为20 mg/kg TID-QID。

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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…’, ‘6488370b0d86975…’, Object(GuzzleHttp\Psr7\Stream))
#22 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘6488370b0d86975…’)
#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…’, ‘6488370b0d86975…’, Object(GuzzleHttp\Psr7\Stream))
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘6488370b0d86975…’)
#22 {main}” width=”1234″ height=”46″>

The same dose can be administered parenterally in dogs (SC, IM, IV) when oral administration is not possible [86].In a previous study [127] it was shown that some dogs develop a tolerance to levetiracetam when used chronically. This phenomenon, the ‘honeymoon effect’, has been documented for other AEDs, e.g. zonisamide and levetiracetam in dogs with epilepsy [127, 129]. Therefore, the introduction of the pulse treatment protocol (an initial dose of 60 mg/kg orally or parenterally after a seizure occurs or preictal signs are recognized by the owner, followed by 20 mg/kg TID until seizures do not occur for 48h) was developed, in order to start treatment only in case of cluster seizures when therapeutic levetiracetam concentrations need to be reached rapidly. The results in the recent study by Packer et al., 2015 [83] supports this clinical approach. Pulse treatment was, however, associated with more side effects compared to maintenance levetiracetam therapy [83]. Levetiracetam is well tolerated and generally safe in dogs. Except for mild sedation, ataxia, decreased appetite and vomiting adverse effects are very rarely described in dogs [79, 127] (Table 2). Levetiracetam has also a different mode of action compared to other AEDs and therefore may be advantageous when polytherapy is instituted. It selectively binds to a presynaptic protein (SVA2), whereby it seems to modulate the release of neurotransmitters [86]. As, in dogs there is no information available regarding a therapeutic range [79], the human target range of 12-46 μg/l can be used as guidance regarding effective concentrations.

在不能口服给药的情况下,犬可通过肠外途径(SC、IM、IV)以相同剂量给药[86]。先前的一项研究[127]表明,一些犬长期使用左乙拉西坦会产生耐受性。这种被称为“蜜月效应(honeymoon effect)”的现象在其他抗癫痫药中也有记载,例如对癫痫犬使用唑尼沙胺和左乙拉西坦时[127,129]。因此,引入脉冲治疗方案(宠主发现抽搐发作或发作前症状后,初始剂量为 60 mg/kg 口服或经非肠道途径给药,随后剂量为20mg /kg TID,直到48小时内不再发生抽搐发作),以便在丛集性抽搐发作时快速达到左乙拉西坦的治疗性血清浓度。Packer等人2015年的最新研究结果[83]支持了这种临床方法。然而,与维持性左乙拉西坦治疗相比,脉冲治疗的副作用更多[83]。左乙拉西坦在犬的耐受性良好,通常是安全的。除了轻微的镇静作用外,犬很少出现运动失调、食欲下降和呕吐等不良反应[79, 127] (表2)。与其他抗癫痫药相比,左乙拉西坦的作用方式也不同,因此在进行多药联合治疗时可能是有利的。它选择性地与突触前膜蛋白(SVA2)结合,从而调节神经递质的释放[86]。由于没有关于犬的治疗性血药浓度范围的信息[79],人类 12-46 μg/L 的靶范围可以作为犬有效血药浓度的一个指导。

<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…’, ’57b88b250f06409…’, Object(GuzzleHttp\Psr7\Stream))
#22 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ’57b88b250f06409…’)
#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…’, ’57b88b250f06409…’, Object(GuzzleHttp\Psr7\Stream))
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ’57b88b250f06409…’)
#22 {main}” width=”1234″ height=”46″>

Studies in humans have shown that concomitant administration of AEDs that induce cytochrome P450 metabolism such as PB, can alter the disposition of levetiracetam [19]. Recently, it has been demonstrated that PB administration significantly alters the pharmacokinetics of levetiracetam in normal dogs [73]. Thus, levetiracetam oral dose may need to be increased or dosing time interval may need to be shortened when concurrently administered with PB [73]. Also in dogs with epilepsy, concurrent administration of PB alone or in combination with KBr increases levetiracetam clearance compared to concurrent administration of KBr alone [78]. Thus, dosage increases might be indicated when utilizing levetiracetam as add-on treatment with PB in dogs [78], preferably guided by levetiracetam serum concentration measurement.

人类研究表明,同时服用含有诱导细胞色素P450代谢(如苯巴比妥)的抗癫痫药可改变左乙拉西坦的代谢[19]。最近有研究表明,苯巴比妥给药可显著改变左乙拉西坦在正常犬体内的药代动力学[73]。因此,与苯巴比妥同时给药时,左乙拉西坦口服剂量可能需要增加或缩短给药时间间隔[73]。同样在癫痫犬中,与单独溴化钾给药相比,同时给药苯巴比妥或溴化钾联合给药可加快左乙拉西坦的清除率[78]。因此,将左乙拉西坦作为犬抗癫痫药附加治疗时,可能需要增加剂量[78],最好以左乙拉西坦血清浓度测量为指导。

<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…’, ‘b6041e6220e63dc…’, Object(GuzzleHttp\Psr7\Stream))
#22 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘b6041e6220e63dc…’)
#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…’, ‘b6041e6220e63dc…’, Object(GuzzleHttp\Psr7\Stream))
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘b6041e6220e63dc…’)
#22 {main}” width=”1234″ height=”46″>

Table 2 Most common reported adverse effects seen in dogs treated with levetiracetam, zonisamide, felbamate, topiramate, gabapentin, and pregabalin (rarely reported and/or idiosyncratic adverse effects are indicated in grey

表2 左乙拉西坦、唑尼沙胺、非尔氨脂、托吡酯、加巴喷丁和普瑞巴林治疗犬最常见的不良反应报告(灰色表示罕见报告和/或特殊不良反应)

<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…’, ‘9571cf1d26dff2c…’, Object(GuzzleHttp\Psr7\Stream))
#22 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘9571cf1d26dff2c…’)
#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…’, ‘9571cf1d26dff2c…’, Object(GuzzleHttp\Psr7\Stream))
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘9571cf1d26dff2c…’)
#22 {main}” width=”412″ height=”546″>
<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…’, ‘2867f256fc35de1…’, Object(GuzzleHttp\Psr7\Stream))
#22 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘2867f256fc35de1…’)
#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…’, ‘2867f256fc35de1…’, Object(GuzzleHttp\Psr7\Stream))
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘2867f256fc35de1…’)
#22 {main}” width=”585″ height=”722″>
<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…’, ‘742543a294138e6…’, Object(GuzzleHttp\Psr7\Stream))
#22 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘742543a294138e6…’)
#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…’, ‘742543a294138e6…’, Object(GuzzleHttp\Psr7\Stream))
#21 C:\wwwroot\upimg.chonwuleyuan.com\getcos.php(10): upload(‘http://i0.hdslb…’, ‘742543a294138e6…’)
#22 {main}” width=”1234″ height=”46″>

THE END
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