Growing interest in the clinical use of cannabidiol (CBD) as adjuvant therapy for pediatric refractory epileptic encephalopathy emphasizes the need for drug treatment optimization. The aim of this study was to characterize the pharmacokinetics of CBD in pediatric patients with refractory epileptic encephalopathy receiving an oil‐based oral solution. To evaluate CBD concentrations, six serial blood samples per patient were collected after the morning dose of CBD, at least 21 days after the beginning of treatment. Twelve patients who received a median (range) dose of 12.2 (5.3‐19.4) mg/kg/d (twice daily) were included in the analysis. Median (range) CBD time to maximum plasma concentration, maximum plasma concentration, and area under the concentration versus time curve up to 6 hours after dosing were 3.2 hours (1.9‐6.2), 49.6 ng/mL (14.4‐302.0), and 226.3 ng ⋅ h/mL (70.5‐861.3), respectively. CBD systemic exposure parameters were in the lower range of previous reports in pediatric patients receiving doses in a similar range. Most of our patients (83%) showed little CBD plasma level fluctuation during a dosing interval, comparable to that encountered after oral administration of an extended release drug delivery system. CDB administration was generally safe and well tolerated, and a novel levothyroxine‐CBD interaction was recorded. Similar to other studies, large interindividual variability in CBD exposure was observed, encouraging the use of CBD therapeutic drug monitoring.

中文翻译：

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大麻二酚在儿童难治性癫痫性脑病中的药代动力学

对大麻二酚 (CBD) 作为小儿难治性癫痫性脑病的辅助治疗的临床应用越来越感兴趣，强调了药物治疗优化的必要性。本研究的目的是表征 CBD 在接受油基口服溶液的难治性癫痫性脑病儿科患者中的药代动力学特征。为了评估 CBD 浓度，在早晨服用 CBD 后，即治疗开始后至少 21 天，每位患者收集了 6 个系列血液样本。12 名接受中位（范围）剂量为 12.2 (5.3-19.4) mg/kg/d（每天两次）的患者被纳入分析。CBD 达到最大血浆浓度的中位（范围）时间、最大血浆浓度和给药后 6 小时的浓度与时间曲线下面积分别为 3.2 小时 (1.9-6.2)、49.6 ng/mL (14.4-302.0)，和 226.3 ng ⋅ h/mL (70.5-861.3)，分别。在接受类似范围剂量的儿科患者中，CBD 全身暴露参数处于先前报告的较低范围内。我们的大多数患者 (83%) 在给药间隔期间的 CBD 血浆水平波动很小，与口服缓释给药系统后遇到的情况相当。CDB 给药通常安全且耐受性良好，并记录了一种新的左旋甲状腺素-CBD 相互作用。与其他研究类似，观察到 CBD 暴露的巨大个体差异，鼓励使用 CBD 治疗药物监测。我们的大多数患者 (83%) 在给药间隔期间的 CBD 血浆水平波动很小，与口服缓释给药系统后遇到的情况相当。CDB 给药通常安全且耐受性良好，并记录了一种新的左旋甲状腺素-CBD 相互作用。与其他研究类似，观察到 CBD 暴露的巨大个体差异，鼓励使用 CBD 治疗药物监测。我们的大多数患者 (83%) 在给药间隔期间的 CBD 血浆水平波动很小，与口服缓释给药系统后遇到的情况相当。CDB 给药通常安全且耐受性良好，并记录了一种新的左旋甲状腺素-CBD 相互作用。与其他研究类似，观察到 CBD 暴露的巨大个体差异，鼓励使用 CBD 治疗药物监测。