ty -jour t1-细胞色素p450-大麻二酚的代谢为活性代谢物7-羟基 - 纳比二醇JF-药物代谢和处置JO -Drug Metab Disbos SP -882 LP -882 LP -891 DO -10.1124/DMD.11亚博体育app24/DMD.10.000350 VL -49 IS-49 IS-49 IS-49 IS-49 IS-4910 Au -Beers,Jessica L. Au -Fu,Dong Au -Jackson,Klarissa D. Y1-2021/10/01 Ur -http://www.3tejia.com/content/49/49/10/10/882.Abstract N2---大麻二酚(CBD)是一种天然存在的非心理毒性植物大麻素,它作为流行的消费产品及其在食品和药物管理中的使用而受到越来越多的关注,用于治疗Lennox-Gastaut综合征和Dravet综合征。先前据报道,CBD主要由CYP2C19和CYP3A4代谢,UDP-葡萄糖醛酸糖基转移酶的贡献较小。与CBD相比,7-羟基-CBD(7-OH-CBD)是具有等值活性的主要活性代谢物。鉴于CYP2C19的多态性性质,我们假设可变的CYP2C19表达可能导致CBD代谢间个体差异至7-OH-CBD。这项研究的目的是进一步表征细胞色素P450酶在CBD代谢中的作用,特别是对活性代谢产物7-OH-CBD的作用,并研究CYP2C19多态性对CBD代谢在基因型人脂质体中的影响。重组细胞色素P450酶和细胞色素P450选择性抑制剂的反应表型实验的结果表明,CYP2C19和CYP2C9均能够将CBD代谢至7-OH-CBD。CYP3A通过7位以外的其他位点的氧化在CBD代谢清除率中起了重要作用。在基因分型人肝微粒体中,7-OH-CBD的形成与CYP2C19活性呈正相关,但与CYP2C19基因型无关。 In a subset of single-donor human liver microsomes with moderate to low CYP2C19 activity, CYP2C9 inhibition significantly reduced 7-OH-CBD formation, suggesting that CYP2C9 may play a greater role in CBD 7-hydroxylation than previously thought. Collectively, these data indicate that both CYP2C19 and CYP2C9 are important contributors in CBD metabolism to the active metabolite 7-OH-CBD.SIGNIFICANCE STATEMENT This study demonstrates that both CYP2C19 and CYP2C9 are involved in CBD metabolism to the active metabolite 7-OH-CBD and that CYP3A4 is a major contributor to CBD metabolism through pathways other than 7-hydroxylation. 7-OH-CBD formation was associated with human liver microsomal CYP2C19 activity, but not CYP2C19 genotype, and CYP2C9 was found to contribute significantly to 7-OH-CBD generation. These findings have implications for patients taking CBD who may be at risk for clinically important cytochrome P450–mediated drug interactions. ER -