Pharmacogenetics of plasma efavirenz exposure after treatment discontinuation: An adult AIDS clinical trials group study
Pharmacogenetics of plasma efavirenz exposure after treatment discontinuation: An adult AIDS clinical trials group study
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DOI：
10.1086/499364
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发表时间：
2006-02-01
影响因子：
11.8
通讯作者：
Acosta, EP
中科院分区：
文献类型：
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作者：
Ribaudo, HJ;Haas, DW;Acosta, EP
背景依法韦仑具有较长的血浆半衰期和较低的耐药遗传屏障。同时停止含依法韦仑方案中所有药物的治疗可能导致功能性依法韦仑单药治疗选择耐药的人类免疫缺陷病毒1型。较低的血浆依法韦仑清除率与细胞色素P450 2B 6基因（CYP 2B 6）多态性（516 G-> T）相关，该多态性在非洲裔美国人个体中比在欧洲裔美国人个体中更常见。我们使用从接受治疗的受试者中获得的数据，描述了这种多态性与预测的依非韦伦停药后血浆浓度-时间曲线之间的关系。使用基于人群的方法估计药代动力学参数。根据受试者特异性估计值预测停药后的浓度。CYP 2B 6基因516位GG（78例）、GT（60例）和TT（14例）基因型患者中，依非韦伦的中位估计半衰期分别为23、27和48 h（P
Background. Efavirenz has a long plasma half-life and a low genetic barrier to resistance. Simultaneously stopping treatment with all agents in efavirenz-containing regimens may result in functional efavirenz monotherapy that selects for drug-resistant human immunodeficiency virus type 1. Lower plasma efavirenz clearance is associated with a cytochrome P450 2B6 gene (CYP2B6) polymorphism (516G -> T) that is more frequent among African American individuals than among European American individuals.Methods. We characterized relationships between this polymorphism and predicted plasma efavirenz concentration-time profiles after discontinuation of therapy with use of data obtained from subjects receiving therapy. Pharmacokinetic parameters were estimated using population-based methods. Concentrations after discontinuation of therapy were predicted from subject-specific estimates.Results. Median estimated efavirenz half-lives were 23, 27, and 48 h for patients with CYP2B6 position 516 GG (78 patients), GT (60), and TT (14) genotypes, respectively (P