Schicht S, Wigger D, Frey H H
Department of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universität Berlin, Germany.
J Vet Pharmacol Ther. 1996 Feb;19(1):27-31. doi: 10.1111/j.1365-2885.1996.tb00004.x.
Oxcarbazepine has been proven to be a promising new antiepileptic drug for the treatment of human epilepsy. Unlike carbamazepine, it is not oxidatively metabolized in humans, and therefore causes almost no induction of hepatic enzymes at clinically effective dosages. Though showing similar efficacy to carbamazepine, it has been reported to cause significantly fewer side-effects. It was the purpose of the present study to determine whether oxcarbazepine might be suitable for the treatment of canine epilepsy. In single-dose experiments, 40 mg/kg oxcarbazepine as a suspension was administered to seven dogs via gastric tube. Plasma concentrations reached peak concentrations of 2.4-8.8 micrograms/mliter at about 1.5 h and declined with an elimination half-life of approximately 4 h. The corresponding concentrations of its metabolite, 10,11-dihydro-10-hydroxycarbamazepine, did not exceed 1 micrograms/mliter. During continued treatment for 8 days, doses of 30 and 50 mg/kg were administered orally in capsules to two dogs three times a day. Plasma concentrations showed a pronounced decline from day 3, and the terminal half-life decreased to 2 h and 1 h. This is considered to be the result of oxcarbazepine inducing its own metabolism. The data reveal that oxcarbazepine, compared with former results with carbamazepine, offers no advantage for the treatment of epileptic dogs.
奥卡西平已被证明是一种有前景的新型抗癫痫药物，用于治疗人类癫痫。与卡马西平不同，它在人体内不会发生氧化代谢，因此在临床有效剂量下几乎不会诱导肝酶。尽管其疗效与卡马西平相似，但据报道其副作用明显较少。本研究的目的是确定奥卡西平是否适用于治疗犬癫痫。在单剂量实验中，通过胃管给7只犬服用40mg/kg奥卡西平混悬液。血浆浓度在约1.5小时时达到2.4 - 8.8微克/毫升的峰值浓度，并以约4小时的消除半衰期下降。其代谢产物10,11 - 二氢 - 10 - 羟基卡马西平的相应浓度不超过1微克/毫升。在持续治疗8天期间，给2只犬每天口服3次胶囊，剂量分别为30mg/kg和50mg/kg。血浆浓度从第3天开始显著下降，终末半衰期降至2小时和1小时。这被认为是奥卡西平诱导自身代谢的结果。数据显示，与之前卡马西平的研究结果相比，奥卡西平在治疗癫痫犬方面没有优势。
