Disposition of Oral Cannabidiol-Rich Cannabis Extracts in Children with Epilepsy.
Disposition of Oral Cannabidiol-Rich Cannabis Extracts in Children with Epilepsy.
复制标题
癫痫儿童口服富含大麻二酚的大麻提取物的处置。
DOI：
10.1007/s40262-020-00869-z
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发表时间：
2020
影响因子：
4.5
通讯作者：
Bajaj,Lalit
中科院分区：
文献类型：
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作者：
Wang,GeorgeSam;Bourne,DavidWA;Klawitter,Jost;Sempio,Cristina;Chapman,Kevin;Knupp,Kelly;Wempe,MichaelF;Borgelt,Laura;Christians,Uwe;Leonard,Jan;Heard,Kennon;Bajaj,Lalit
背景和目的尽管证据有限，但富含大麻二酚的大麻提取物已广泛用于儿科。随着使用的增加，确定儿童人群中这些提取物中大麻二酚的基本药代动力学参数至关重要。本研究的目的是确定的处置口服大麻二酚大麻提取物和药物相互作用的儿童与小儿epilepsy.MethodsWe进行了一项前瞻性观察研究，评估处置口服大麻二酚的儿童（< 18岁）接受大麻二酚提取物癫痫。受试者在口服大麻二酚给药后进行了连续抽血。确定了大麻二酚及其代谢物以及抗惊厥药物的浓度。结果二十九名患者具有足够的药代动力学数据并被纳入分析中。沿着。平均年龄为9.7岁（标准差4.3），17例患者（59%）为男性。中位血浆大麻二酚浓度峰值为13.1 ng/mL（四分位数范围6.8-39.3 ng/mL）;中位达峰时间为2.0 h（四分位数范围2.0-4.0 h）。口服大麻二酚的平均急性消除半衰期为6.2小时（标准差1.8小时）。当储存0.6-3.1年时，观察到大麻二酚浓度的降解半衰期为533天。大麻二酚的药代动力学参数有一定的影响时，大麻二酚共同管理唑尼沙胺（消除速率常数和V1）和左乙拉西坦（消除速率常数）。ConclusionsIn儿科患者使用口服大麻二酚丰富的大麻提取物癫痫，血浆大麻二酚的峰值浓度和平均急性消除半衰期的时间短于成人的报告。唑尼沙胺和左乙拉西坦联合给药对大麻二酚药代动力学参数有一定影响。在长期储存中观察到血浆大麻二酚降解。临床registrationClinicalTrials.gov标识号NCT 02447198。
Background and ObjectivesDespite limited evidence, cannabidiol-rich cannabis extracts have been popularly used in pediatrics. With increased use, it is critical to determine basic pharmacokinetic parameters of cannabidiol in these extracts in the pediatric population. The objective of this study was to determine the disposition of oral cannabidiol cannabis extracts and drug interactions in children with pediatric epilepsy.MethodsWe conducted a prospective observational study evaluating the disposition of oral cannabidiol in children (< 18 years of age) receiving cannabidiol extracts for epilepsy. Subjects underwent serial blood draws after oral cannabidiol administration. Cannabidiol and metabolites, along with anticonvulsant concentrations were determined.ResultsTwenty-nine patients had sufficient pharmacokinetic data and were included in the analysis. Mean age was 9.7 years (standard deviation 4.3) and 17 patients (59%) were male. Median peak plasma cannabidiol concentrations was 13.1 ng/mL (interquartile range 6.8–39.3 ng mL); median time to peak of 2.0 h (interquartile range 2.0–4.0 h). Mean acute elimination half-life of oral cannabidiol was 6.2 h (standard deviation 1.8 h). There was an observed half-life of degradation of 533 days noted for cannabidiol concentrations when stored for 0.6–3.1 years. There was some impact on cannabidiol pharmacokinetic parameters when cannabidiol was co-administered with zonisamide (elimination rate constant and V1) and levetiracetam (elimination rate constant).ConclusionsIn pediatric patients using oral cannabidiol-rich cannabis extract for epilepsy, the time to peak concentration of plasma cannabidiol and average acute elimination half-life were shorter than those reported for adults. Co-administration of zonisamide and levetiracetam had some impact on cannabidiol pharmacokinetic parameters. There was an observed degradation of plasma cannabidiol in long-term storage.Clinical registrationClinicalTrials.gov Identifer no. NCT02447198.