Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
Ther Drug Monit. 2009 Aug;31(4):527-30. doi: 10.1097/FTD.0b013e3181ad74a4.
Cytochrome P450 2B6 (CYP2B6) is the main metabolizing pathway for efavirenz (EFV), the prescription of which is associated with neurologic side effects. The authors conducted a study on the prevalence of CYP2B6 polymorphism, profile of side effects, and pharmacokinetics of EFV in a group of human immunodeficiency virus (HIV)-infected southern Chinese. Patients with HIV were recruited at the Shenzhen City Third People's Hospital, China. The prevalence of CYP2B6 G516T and plasma EFV concentration were determined. Pharmacokinetics was assessed using blood samples of selected patients at time 0, 1, 2, 4, 8, 12, and 24 hours after the last dose of EFV. Between October 2007 and June 2008, 79 Chinese patients with HIV were recruited. Sequencing of CYP2B6 at position 516 gave 42 GG, 34 GT, and 3 TT genotypes, with corresponding mean spot plasma EFV level of 3.4, 4.1, and 8.1 mg/L, respectively. The allelic frequency of 516 G>T was 0.25. Univariate analysis showed that plasma EFV level correlated with genotype (P = 0.02). Eighteen patients completed the pharmacokinetic study: TT genotype gave the longest half-life (t 1/2), highest plasma EFV concentration, and largest area under the curve. The volume of distribution per surface area (Vd ss), total clearance (Cltot), and elimination rate constant (ke) were the lowest. There was no association between the occurrence of side effects and the EFV concentration (chi2 test, P > 0.05). The EFV pharmacokinetics of TT genotype differed significantly from GG and GT genotypes. Accumulation of EFV may potentially occur over time, causing toxicity in TT and GT genotypes.
细胞色素 P450 2B6（CYP2B6）是依非韦伦（EFV）的主要代谢途径，EFV 的处方与神经副作用有关。作者在中国南方的一组艾滋病毒（HIV）感染者中进行了 CYP2B6 多态性、副作用谱和 EFV 药代动力学的研究。在深圳市第三人民医院招募了 HIV 患者。确定了 CYP2B6 G516T 的流行率和血浆 EFV 浓度。使用选定患者在最后一次 EFV 剂量后 0、1、2、4、8、12 和 24 小时的血样评估药代动力学。2007 年 10 月至 2008 年 6 月，招募了 79 名中国 HIV 患者。在位置 516 处对 CYP2B6 进行测序得到 42 个 GG、34 个 GT 和 3 个 TT 基因型，相应的平均斑点血浆 EFV 水平分别为 3.4、4.1 和 8.1mg/L。516G>T 的等位基因频率为 0.25。单变量分析表明，血浆 EFV 水平与基因型相关（P=0.02）。18 名患者完成了药代动力学研究：TT 基因型半衰期最长（t1/2）、血浆 EFV 浓度最高、曲线下面积最大。体表面积分布容积（Vdss）、总清除率（Cltot）和消除率常数（ke）最低。副作用的发生与 EFV 浓度无关（卡方检验，P>0.05）。TT 基因型的 EFV 药代动力学与 GG 和 GT 基因型有显著差异。EFV 的蓄积可能随时间而发生，导致 TT 和 GT 基因型的毒性。
