Highly purified cannabidiol (CBD) has demonstrated efficacy with an acceptable safety profile in patients with Lennox‐Gastaut syndrome or Dravet syndrome in randomized, double‐blind, add‐on, controlled phase 3 trials. It is important to consider the possibility of drug‐drug interactions (DDIs). Here, we review six trials of CBD (Epidiolex/Epidyolex; 100 mg/mL oral solution) in healthy volunteers or patients with epilepsy, which investigated potential interactions between CBD and enzymes involved in drug metabolism of common antiseizure drugs (ASDs). CBD did not affect CYP3A4 activity. Induction of CYP3A4 and CYP2C19 led to small reductions in exposure to CBD and its major metabolites. Inhibition of CYP3A4 activity did not affect CBD exposure and caused small increases in exposure to CBD metabolites. Inhibition of CYP2C19 activity led to a small increase in exposure to CBD and small decreases in exposure to CBD metabolites. One potentially clinically important DDI was identified: combination of CBD and clobazam (CLB) did not affect CBD or CLB exposure, but increased exposure to major metabolites of both compounds. Reduction of CLB dose may be considered if adverse reactions known to occur with CLB are experienced when it is coadministered with CBD. There was a small increase of exposure to stiripentol (STP) when coadministered with CBD. STP had no effect on CBD exposure but led to minor decreases in exposure to CBD metabolites. Combination of CBD and valproate (VPA) did not cause clinically important changes in the pharmacokinetics of either drug, or 2‐propyl‐4‐pentenoic acid. Concomitant VPA caused small increases in exposure to CBD metabolites. Dose adjustments are not likely to be necessary when CBD is combined with STP or VPA. The safety results from these trials were consistent with the known safety profile of CBD. These trials indicate an overall low potential for DDIs between CBD and other ASDs, except for CLB.

中文翻译：

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研究大麻二酚与酶诱导剂或抑制剂或常见抗癫痫药之间药物相互作用的试验的临床意义

在随机、双盲、附加、对照 3 期试验中，高度纯化的大麻二酚 (CBD) 已证明对 Lennox-Gastaut 综合征或 Dravet 综合征患者的疗效和可接受的安全性。考虑药物相互作用 (DDI) 的可能性很重要。在这里，我们回顾了 CBD（Epidiolex/Epidyolex；100 mg/mL 口服溶液）在健康志愿者或癫痫患者中的六项试验，这些试验研究了 CBD 与参与常见抗癫痫药 (ASD) 药物代谢的酶之间的潜在相互作用。CBD 不影响 CYP3A4 活性。CYP3A4 和 CYP2C19 的诱导导致 CBD 及其主要代谢物的暴露量小幅减少。CYP3A4 活性的抑制不影响 CBD 暴露，并导致 CBD 代谢物的暴露略有增加。CYP2C19 活性的抑制导致对 CBD 的暴露略有增加，而对 CBD 代谢物的暴露略有减少。确定了一种具有潜在临床意义的 DDI：CBD 和氯巴占 (CLB) 的组合不影响 CBD 或 CLB 暴露，但增加了对两种化合物主要代谢物的暴露。如果在与 CBD 共同给药时经历了已知与 CLB 发生的不良反应，则可以考虑减少 CLB 剂量。与 CBD 共同给药时，司替戊醇 (STP) 的暴露量略有增加。STP 对 CBD 暴露没有影响，但导致对 CBD 代谢物的暴露略有减少。CBD 和丙戊酸 (VPA) 的组合不会导致任何一种药物或 2-丙基-4-戊烯酸的药代动力学发生临床上重要的变化。伴随的 VPA 导致 CBD 代谢物的暴露量略有增加。当 CBD 与 STP 或 VPA 结合使用时，可能不需要调整剂量。这些试验的安全性结果与 CBD 的已知安全性一致。这些试验表明 CBD 和其他 ASD 之间 DDI 的总体可能性较低，但 CLB 除外。