Burger David, van der Heiden Ilse, la Porte Charles, van der Ende Marchina, Groeneveld Paul, Richter Clemens, Koopmans Peter, Kroon Frank, Sprenger Herman, Lindemans Jan, Schenk Paul, van Schaik Ron
Radboud University Medical Center Nijmegen, the Netherlands.
Br J Clin Pharmacol. 2006 Feb;61(2):148-54. doi: 10.1111/j.1365-2125.2005.02536.x.
To characterize the demographic and pharmacogenetic factors that influence interpatient variability in the plasma concentrations of the HIV non-nucleoside reverse transcriptase inhibitor efavirenz.
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 CYP2B66 and CYP2B67) which is associated with low CYP2B6 activity.
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.
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.
明确影响艾滋病病毒非核苷类逆转录酶抑制剂依非韦伦血浆浓度患者间变异性的人口统计学和药物遗传学因素。
回顾了2002年和2003年我们的治疗药物监测服务中所有检测依非韦伦的样本数据。记录了性别、年龄、体重、身高、种族、激素避孕药使用情况（部分患者）以及采样与最后一次服药之间的时间。进行聚合酶链反应-限制性片段长度多态性分析以检测细胞色素P450 2B6（CYP2B6）C1459T变异体（存在于CYP2B66和CYP2B67中），该变异体与低CYP2B6活性相关。
本分析共纳入255例患者。依非韦伦血浆浓度中位数为2.50（四分位间距：1.85 - 3.55）mg·l⁻¹。8例患者（3.1%）被认为血浆浓度低于治疗水平（<1.0 mg·l⁻¹），48例患者（18.9%）依非韦伦浓度中毒（>4.0 mg·l⁻¹）。在多变量分析中，性别、最后一次服药后的时间和种族是与依非韦伦血浆浓度显著相关的仅有的因素。未观察到体重、激素避孕药使用情况以及CYP2B6 C1459T多态性的影响。
性别和种族是决定依非韦伦血浆浓度患者间变异性的重要因素，不受CYP2B6 C1459T多态性存在的影响。医生应特别警惕女性和非白种人患者中依非韦伦所致毒性的迹象。
