卡马西平
药代动力学
化学
药理学
代谢物
抗惊厥药
癫痫
医学
生物化学
精神科
作者
Armel Stockis,Hugues Chanteux,Maria de Lurdes Pereira Rosa,Paul Rolan
标识
DOI:10.1016/j.eplepsyres.2015.03.003
摘要
This phase I, open-label study investigated the effects of steady-state brivaracetam administration on steady-state pharmacokinetics of carbamazepine, and steady-state carbamazepine administration on single-dose and steady-state pharmacokinetics of brivaracetam, in 14 healthy participants who received brivaracetam 200 mg single doses on days 1 and 22, and 200 mg twice daily (bid) on days 24–35; and were titrated to carbamazepine 300 mg bid on days 4–35. Brivaracetam did not significantly alter carbamazepine area under the plasma concentration–time curve (AUC) over a dosing interval, but resulted in a 2.6-fold increase in carbamazepine-epoxide. Carbamazepine decreased brivaracetam AUC by 29%, while hydroxy-brivaracetam metabolite was increased by 17%. Urinary 6β-hydroxycortisol/cortisol ratio was unchanged by brivaracetam, but was increased 3-fold by carbamazepine. In vitro hydrolysis of carbamazepine-epoxide in human hepatocytes was inhibited by brivaracetam, with an IC50 of 8.2 μM. Brivaracetam 200 mg bid was predicted to increase carbamazepine-epoxide by 2.3-fold, in close agreement with the observed value. In conclusion, brivaracetam did not modify carbamazepine exposure but increased carbamazepine-epoxide. Carbamazepine modestly decreased brivaracetam exposure and increased oxidative metabolism.
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