GWPharmaceuticals高纯度大麻二酚口服液的配方在美国被批准用于年龄≥2岁的患者与Lennox-Gastaut和Dravet综合征相关的癫痫发作,对于哪个clobazam,stiripentol,丙戊酸盐是常用的抗癫痫药物。这个开放标签,固定序列,药物-药物相互作用,健康志愿者试验研究了大麻二酚对氯巴赞(和N-去甲基氯巴赞)稳态药代动力学的影响,stiripentol,和丙戊酸盐;氯巴赞的相互作用,stiripentol,和丙戊酸对大麻二酚及其主要代谢产物(7-羟基大麻二酚[7-OH-CBD]和7-羧基大麻二酚[7-COOH-CBD])的影响;与每种抗癫痫药物共同给药时,大麻二酚的安全性和耐受性。伴随大麻二酚对氯巴赞暴露几乎没有影响(最大浓度[Cmax]和浓度-时间曲线下面积[AUC],1.2-fold),N-去甲基氯巴赞暴露增加(Cmax和AUC,3.4折),stiripentol暴露略有增加(Cmax,1.3倍;AUC,1.6倍),而未观察到对丙戊酸盐暴露的临床相关影响。氯巴赞与大麻二酚合并增加7-OH-CBD暴露(Cmax,1.7倍;AUC,1.5-fold),没有显着的7-COOH-CBD或大麻二酚增加。Stiripentol将7-OH-CBD暴露减少了29%,将7-COOH-CBD暴露减少了13%。丙戊酸对大麻二酚或其代谢物没有影响。大麻二酚的耐受性中等,与clobazam共同给药时报告的不良事件发生率相似,stiripentol,或者丙戊酸盐。没有死亡,严重不良事件,怀孕,或其他具有临床意义的安全性发现。
GW Pharmaceuticals\' formulation of highly purified cannabidiol oral solution is approved in the United States for seizures associated with Lennox-Gastaut and Dravet syndromes in patients aged ≥2 years, for which clobazam,
stiripentol, and valproate are commonly used antiepileptic drugs. This open-label, fixed-sequence, drug-drug interaction, healthy volunteer
trial investigated the impact of cannabidiol on steady-state pharmacokinetics of clobazam (and N-desmethylclobazam),
stiripentol, and valproate; the reciprocal effect of clobazam,
stiripentol, and valproate on cannabidiol and its major metabolites (7-hydroxy-cannabidiol [7-OH-CBD] and 7-carboxy-cannabidiol [7-COOH-CBD]); and cannabidiol safety and tolerability when coadministered with each antiepileptic drug. Concomitant cannabidiol had little effect on clobazam exposure (maximum concentration [Cmax ] and area under the concentration-time curve [AUC], 1.2-fold), N-desmethylclobazam exposure increased (Cmax and AUC, 3.4-fold), stiripentol exposure increased slightly (Cmax , 1.3-fold; AUC, 1.6-fold), while no clinically relevant effect on valproate exposure was observed. Concomitant clobazam with cannabidiol increased 7-OH-CBD exposure (Cmax , 1.7-fold; AUC, 1.5-fold), without notable 7-COOH-CBD or cannabidiol increases.
Stiripentol decreased 7-OH-CBD exposure by 29% and 7-COOH-CBD exposure by 13%. There was no effect of valproate on cannabidiol or its metabolites. Cannabidiol was moderately well tolerated, with similar incidences of adverse events reported when coadministered with clobazam, stiripentol, or valproate. There were no deaths, serious adverse events, pregnancies, or other clinically significant safety findings.