Interactions between cannabidiol and commonly used antiepileptic drugs
Interactions between cannabidiol and commonly used antiepileptic drugs
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DOI：
10.1111/epi.13852
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发表时间：
2017-09-01
期刊：
影响因子：
5.6
通讯作者：
Szaflarski, Jerzy P.
中科院分区：
文献类型：
--
作者：
Gaston, Tyler E.;Bebin, E. Martina;Szaflarski, Jerzy P.
目的：通过一项开放标签安全性研究，确定大麻二酚（CBD; Epidiolex）制剂与常用抗癫痫药物（aed）之间潜在的药代动力学相互作用。监测血清水平以确定CBD和aed之间的相互作用。方法：在39名成人和42名儿童中，CBD剂量开始为5mg /kg/天，每2周增加5mg /kg/天，直到最大50mg /kg/天。在CBD开始前的基线和大多数研究访问时获得血清AED水平。如果确定临床症状或实验室结果与潜在的相互作用有关，则调整AED剂量。使用混合程序来确定19种aed的血清水平是否随着CBD剂量的增加而发生显著变化。在初始分析中观察到的具有相互作用的抗癫痫药，绘制了血清水平随时间的平均变化。进行亚分析以确定参与者的镇静频率是否与平均血清n -去甲基氯巴唑水平有关，以及在服用丙戊酸盐的参与者中，天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）水平是否不同。结果：血清托吡酯、鲁非胺和n -去甲基氯巴唑水平随cbd剂量的增加而升高，氯巴唑水平下降（p < 0.01）。成人血清中唑尼沙胺（p = 0.02）和埃斯卡巴西平（p = 0.04）水平随CBD剂量增加而升高。除氯巴唑和去甲基氯巴唑外，所有记录的平均水平变化均在可接受的治疗范围内。成人n -去甲基氯巴唑水平越高，镇静发生的频率越高（p = 0.02），同时服用丙戊酸钠的患者AST/ALT水平明显越高（p < 0.01）。意义：氯巴唑、鲁非那胺、托吡酯、唑尼沙胺和埃斯卡巴西平的血清水平有显著变化。同时服用丙戊酸盐的参与者肝功能检查结果异常。本研究强调了在CBD治疗期间监测血清AED水平和LFTs的重要性。
Objective: To identify potential pharmacokinetic interactions between the pharmaceutical formulation of cannabidiol (CBD; Epidiolex) and the commonly used antiepileptic drugs (AEDs) through an open-label safety study. Serum levels were monitored to identify interactions between CBD and AEDs.Methods: In 39 adults and 42 children, CBD dose was started at 5 mg/kg/day and increased every 2 weeks by 5 mg/kg/day up to a maximum of 50 mg/kg/day. Serum AED levels were obtained at baseline prior to CBD initiation and at most study visits. AED doses were adjusted if it was determined that a clinical symptom or laboratory result was related to a potential interaction. The Mixed Procedure was used to determine if there was a significant change in the serum level of each of the 19 AEDs with increasing CBD dose. AEDs with interactions seen in initial analysis were plotted for mean change in serum level over time. Subanalyses were performed to determine if the frequency of sedation in participants was related to the mean serum N-desmethyl-clobazam level, and if aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were different in participants taking concomitant valproate.Results: Increases in topiramate, rufinamide, and N-desmethylclobazam and decrease in clobazam (all p < 0.01) serumlevels were seen with increasing CBDdose. Increases in serum levels of zonisamide (p = 0.02) and eslicarbazepine (p = 0.04) with increasing CBD dose were seen in adults. Except for clobazam and desmethylclobazam, all noted mean level changes were within the accepted therapeutic range. Sedation wasmore frequent with higher N-desmethylclobazamlevels in adults (p = 0.02), and AST/ALT levels were significantly higher in participants taking concomitant valproate (p < 0.01).Significance: Significantly changed serum levels of clobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine were seen. Abnormal liver function test results were noted in participants taking concomitant valproate. This study emphasizes the importance of monitoring serum AED levels and LFTs during treatment with CBD.