Department of Clinical and Experimental Epilepsy, UCL-Institute of Neurology, Queen Square, London, United Kingdom; Epilepsy Society, Chalfont Centre for Epilepsy, Chalfont St Peter, United Kingdom.
Epilepsia. 2015 Jan;56(1):12-27. doi: 10.1111/epi.12865. Epub 2014 Dec 13.
The clinical pharmacology profile of a drug critically determines its therapeutics, and this review summarizes the characteristics associated with the antiepileptic drug (AED) perampanel. A PubMed literature search was performed for perampanel. Congress abstract data are included where necessary and Eisai Ltd provided access to unpublished data on file. After oral ingestion, perampanel is rapidly absorbed and peak plasma concentrations occur 0.5-2.5 h later; its bioavailability is 100%. Although the rate of perampanel absorption is slowed by food co-ingestion, the extent absorbed remains unchanged; therefore, perampanel can be administered without regard to meal times. The pharmacokinetics of perampanel are linear and predictable over the clinically relevant dose range (2-12 mg); perampanel is 95% protein-bound to albumin and α1-acid glycoprotein. Perampanel is extensively metabolized (>90%) in the liver, primarily by cytochrome P450 (CYP) 3A4, to various pharmacologically inactive metabolites. In healthy volunteers, the apparent terminal half-life is ~105 h, whereas the calculated effective half-life is 48 h. These half-life values allow for once-daily dosing, which will aid patient compliance and in the event of a missed dose, will have minimal impact on seizure control. In healthy volunteers prescribed carbamazepine, half-life decreases to 25 h. Clearance values are not significantly different in adolescents (13.0 ml/min) and the elderly (~10.5 ml/min) compared with adults (10.9 ml/min). Perampanel has minimal propensity to cause pharmacokinetic interactions. However, it is the target of such interactions and CYP3A4-inducing AEDs enhance its clearance; this can be used to advantage because dose titration can be faster and thus optimum therapeutic outcome can be achieved sooner. Perampanel 12 mg, but not 4 or 8 mg, enhances the metabolism of the progesterone component of the oral contraceptive pill, necessitating the need for an additional reliable contraceptive method. Overall, perampanel has a favorable clinical pharmacology profile, which should aid its clinical use.
药物的临床药理学特征对其治疗效果至关重要，本综述总结了与抗癫痫药（AED）吡仑帕奈相关的特征。对吡仑帕奈进行了 PubMed 文献检索。必要时纳入了大会摘要数据，卫材株式会社提供了存档的未发表数据。口服后，吡仑帕奈迅速吸收， 0.5-2.5 小时后达到血浆峰浓度；其生物利用度约为 100%。尽管食物同服会减缓吡仑帕奈的吸收速度，但吸收程度保持不变；因此，无需考虑进餐时间给予吡仑帕奈。吡仑帕奈的药代动力学在临床相关剂量范围内（2-12mg）呈线性和可预测；吡仑帕奈 95%与白蛋白和α1-酸性糖蛋白结合。吡仑帕奈在肝脏中被广泛代谢（>90%），主要通过细胞色素 P450（CYP）3A4 代谢为多种无药理活性的代谢物。在健康志愿者中，表观终末半衰期约为 105 小时，而计算的有效半衰期为 48 小时。这些半衰期值允许每日一次给药，这将有助于提高患者的依从性，并且在漏服药物的情况下，对癫痫控制的影响最小。在服用卡马西平的健康志愿者中，半衰期降至 25 小时。与成年人（10.9ml/min）相比，青少年（13.0ml/min）和老年人（10.5ml/min）的清除率值无显著差异。吡仑帕奈引起药代动力学相互作用的可能性较小。然而，它是这种相互作用的靶点，并且 CYP3A4 诱导的 AED 增强了其清除率；这可以被利用，因为剂量滴定可以更快，从而可以更快地达到最佳治疗效果。吡仑帕奈 12mg，但不是 4 或 8mg，增强了口服避孕药中孕激素成分的代谢，需要使用另一种可靠的避孕方法。总体而言，吡仑帕奈具有良好的临床药理学特征，这应有助于其临床应用。
