Efavirenz is a non-nucleoside reverse transcriptase inhibitor used as first-line therapy for the treatment of HIV infection. Cytochrome P450 (CYP) CYP2B6 G516T (rs3745274) is a well-known predictor of efavirenz disposition. Dose adjustment based on G516T variant has been shown to be beneficial. However, this variant cannot explain the entire variability of efavirenz pharmacokinetics. In this study, we evaluated the influence of 11 single-nucleotide polymorphisms (SNPs) in CYP2B6, CYP2A6, CYP3A and ABCB1 (ATP-binding cassette sub-family B member 1) on the pharmacokinetics and safety of efavirenz after single oral dose administration to 47 healthy volunteers. We designed and validated a CYP2B6 activity score model based on two CYP2B6 SNPs (G516T and rs4803419) that predicted efavirenz disposition better than G516T alone.

Efavirenz是一种非核苷类逆转录酶抑制剂，被用作治疗HIV感染的一线疗法。细胞色素P450（CYP）CYP2B6 G516T（rs3745274）是依法韦仑治疗的众所周知的预测因子。已经证明基于G516T变体的剂量调整是有益的。但是，该变体不能解释依非韦伦药代动力学的全部可变性。在这项研究中，我们评估了CYP2B6，CYP2A6，CYP3A和ABCB1（ATP结合盒B亚家族B成员1）中11种单核苷酸多态性（SNPs）对依法韦仑单次口服给药后药代动力学和安全性的影响。 47名健康志愿者。我们基于两个CYP2B6设计并验证了CYP2B6活动评分模型 预测依非韦伦治疗的SNP（G516T和rs4803419）比单独使用G516T更好。