Interpatient variability in the pharmacokinetics of the HIV non-nucleoside reverse transcriptase inhibitor efavirenz:: the effect of gender, race, and CYP2B6 polymorphism
Interpatient variability in the pharmacokinetics of the HIV non-nucleoside reverse transcriptase inhibitor efavirenz:: the effect of gender, race, and CYP2B6 polymorphism
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DOI：
10.1111/j.1365-2125.2005.02536.x
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发表时间：
2006-02-01
影响因子：
3.4
通讯作者：
van Schaik, R
中科院分区：
文献类型：
--
作者：
Burger, D;van der Heiden, I;van Schaik, R
目的描述人口统计学和药物遗传学因素，影响患者间变异的血浆浓度的HIV非核苷类逆转录酶抑制剂efavirenz.Methods数据从所有样本分析efavirenz在我们的TDM服务在2002年和2003年进行了审查。记录性别、年龄、体重、身高、人种、激素避孕药使用（在患者子集中）以及采样与末次给药之间的时间。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析方法检测与CYP 2B 6活性低下相关的细胞色素P450 2B 6（CYP 2B 6）C1459 T变异（存在于CYP 2B 6 *6和CYP 2B 6 *7中）。中位血浆依法韦仑浓度为2.50（四分位数范围：1.85-3.55）mg l（-1）。8名患者（3.1%）被认为具有亚治疗血浆浓度（< 1.0 mg l（-1））和48名（18.9%）具有毒性依法韦仑浓度（> 4.0 mg l（-1））。在多变量分析中，性别、末次给药后时间和种族是唯一与血浆依法韦仑浓度显著相关的因素。没有观察到影响体重，激素避孕药的使用，和CYP 2B 6 C1459 T polymorphis.Conclusions的存在下，性别和种族是重要的因素，在确定患者间的血浆依法韦仑浓度的变异性不受CYP 2B 6 C1459 T多态性的存在。医生应特别警惕女性和非高加索患者中依法韦仑诱导的毒性体征。
Aims To characterize the demographic and pharmacogenetic factors that influence interpatient variability in the plasma concentrations of the HIV non-nucleoside reverse transcriptase inhibitor efavirenz.Methods Data from all samples analyzed for efavirenz in our TDM service in 2002 and 2003 were reviewed. Information on gender, age, body weight, height, race, hormonal contraceptive use (in a subset of patients), and time between sampling and last intake was recorded. PCR-restriction fragment length polymorphism analysis was performed to detect the cytochrome P450 2B6 (CYP2B6) C1459T variant (present in CYP2B6*6 and CYP2B6*7) which is associated with low CYP2B6 activity.Results A total of 255 patients were included in this analysis. The median plasma efavirenz concentration was 2.50 (interquartile range: 1.85-3.55) mg l(-1). Eight patients (3.1%) were considered to have a subtherapeutic plasma concentration (< 1.0 mg l(-1)) and 48 (18.9%) a toxic efavirenz concentration (> 4.0 mg l(-1)). Gender, time after last intake, and race were the only factors that were significantly related to plasma efavirenz concentration in a multivariate analysis. No influence was observed for body weight, hormonal contraceptive use, and the presence of the CYP2B6 C1459T polymorphism.Conclusions Gender and race are important factors in determining interpatient variability in plasma efavirenz concentrations which were unaffected by the presence of the CYP2B6 C1459T polymorphism. Physicians should be particularly alert for signs of efavirenz-induced toxicity in females and non-Caucasian patients.