Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy
Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy
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DOI：
10.1111/epi.13060
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发表时间：
2015-08-01
期刊：
影响因子：
5.6
通讯作者：
Thiele, Elizabeth A.
中科院分区：
文献类型：
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作者：
Geffrey, Alexandra L.;Pollack, Sarah F.;Thiele, Elizabeth A.
在一项扩大使用的研究性新药（IND）试验中，大麻二酚（CBD）正在被研究作为儿童难治性癫痫的可能辅助治疗。在试验的25例受试者中，13例接受氯巴占（CLB）治疗。由于CLB和CBD都代谢的细胞色素P450（CYP 1A 1）途径，我们预测药物相互作用，我们评估在this article.MethodsThirteen与难治性癫痫伴随CLB和CBD IND 119876的主题被列入本研究。收集每例受试者的人口统计学信息，包括年龄、性别和癫痫发作病因，以及伴随使用的抗癫痫药物（AED）。CLB，N-去甲基氯巴占（norclobazam; nCLB）和CBD水平在CBD治疗过程中进行测量。在基线和CBD治疗的第4周和第8周记录CLB剂量。副作用monitored.ResultsWe报告升高CLB和nCLB水平在这些科目。CLB水平的平均（标准差[SD]）增加为60 +/- 80%（4周时的95%置信区间（CI）[-2-91%]）; nCLB水平的平均增加为500 +/- 300%（4周时的95% CI [+90-610%]）。13名受试者中有9名的癫痫发作减少>50%，对应于70%的应答率。尽管在CBD治疗过程中，13名受试者中有10名（77%）的CLB剂量减少，但CLB和nCLB水平增加以及癫痫发作频率降低。13名受试者中有10名（77%）报告了副作用，但随着CLB剂量的减少而减轻。尽管如此，CBD是接受CLB治疗的难治性癫痫患者的安全有效的治疗方法。
ObjectiveUnder an expanded access investigational new drug (IND) trial, cannabidiol (CBD) is being studied as a possible adjuvant treatment of refractory epilepsy in children. Of the 25 subjects in the trial, 13 were being treated with clobazam (CLB). Because CLB and CBD are both metabolized in the cytochrome P450 (CYP) pathway, we predicted a drug-drug interaction, which we evaluate in this article.MethodsThirteen subjects with refractory epilepsy concomitantly taking CLB and CBD under IND 119876 were included in this study. Demographic information was collected for each subject including age, sex, and etiology of seizures, as well as concomitant antiepileptic drugs (AEDs). CLB, N-desmethylclobazam (norclobazam; nCLB), and CBD levels were measured over the course of CBD treatment. CLB doses were recorded at baseline and at weeks 4 and 8 of CBD treatment. Side effects were monitored.ResultsWe report elevated CLB and nCLB levels in these subjects. The mean (standard deviation [SD]) increase in CLB levels was 60 +/- 80% (95% confidence interval (CI) [-2-91%] at 4weeks); the mean increase in nCLB levels was 500 +/- 300% (95% CI [+90-610%] at 4weeks). Nine of 13 subjects had a >50% decrease in seizures, corresponding to a responder rate of 70%. The increased CLB and nCLB levels and decreases in seizure frequency occurred even though, over the course of CBD treatment, CLB doses were reduced for 10 (77%) of the 13 subjects. Side effects were reported in 10 (77%) of the 13 subjects, but were alleviated with CLB dose reduction.SignificanceMonitoring of CLB and nCLB levels is necessary for clinical care of patients concomitantly on CLB and CBD. Nonetheless, CBD is a safe and effective treatment of refractory epilepsy in patients receiving CLB treatment.