TY -的T1 -细胞色素P450-Catalyzed大麻二酚的代谢活性代谢物7-Hydroxy-Cannabidiol JF -药物代谢和性格乔-药物金属底座Dispos SP - 882 LP - 891 - 10.1124 / dm亚博体育appd.120.000350六世- 49 - 10盟是啤酒,杰西卡·l . AU -傅董AU -杰克逊,Klarissa d Y1 - 2021/10/01 UR - //www.3tejia.com/content/49/10/882.abstract N2 -大麻二酚(CBD)是一种天然nonpsychotoxic phytocannabinoid,已得到了越来越多的关注,成为一种热门的消费产品,它的使用在食品和药品管理局批准了Epidiolex (CBD口服溶液)治疗Lennox-Gastaut综合征和Dravet综合征。此前有报道称,CBD主要由CYP2C19和CYP3A4代谢,udp -葡萄糖醛酸转移酶也有少量贡献。7-羟基-CBD (7-OH-CBD)是主要的活性代谢物,与CBD活性相当。鉴于CYP2C19的多态性,我们假设可变的CYP2C19表达可能导致7-OH-CBD代谢的个体间差异。本研究的目的是进一步研究细胞色素P450酶在CBD代谢中的作用,特别是活性代谢物7-OH-CBD,并研究CYP2C19多态性对基因型人肝微粒体中CBD代谢的影响。重组细胞色素P450酶和细胞色素P450选择性化学抑制剂的反应表型实验结果表明,CYP2C19和CYP2C9均能代谢7-OH-CBD。CYP3A在CBD代谢清除中起主要作用,通过氧化除7位以外的位点。在基因型的人肝微粒体中,7-OH-CBD的形成与CYP2C19活性呈正相关,而与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 -