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目的研究中国健康人CYP2B6*6基因多态性对依法韦仑药动学的影响。方法应用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)将40名健康中国志愿者分为3组:CYP2B6*1/*1组(n=29),CYP2B6*1/*6组(n=8)和CYP2B6*6/*6组(n=3)。受试者单剂量口服依法韦仑600 mg,收集给药后336 h内的一系列血样,用HPLC-MS/MS法测定依法韦仑的血药浓度并进行药动学分析。结果与CYP2B6*1/*1组相比,CYP2B6*6/*6基因型的志愿者的依法韦仑血药浓度较高(P<0.05);CYP2B6*1/*6组与CYP2B6*6/*6组的主要药动学参数(t1/2、AUC0-336 h和AUC0-∞)均存在显著差异(P<0.05或P<0.01);CYP2B6*1/*6组与CYP2B6*6/*6组的tmax和ρmax无显著差异(P>0.05)。结论 CYP2B6*6等位基因突变能引起代谢表型的改变,影响依法韦仑在中国健康人群的代谢。根据基因型制定个体化给药方案有助于依法韦仑的合理使用。
Objective To study the effect of CYP2B6 * 6 gene polymorphism on the efavirenz pharmacokinetics in healthy Chinese. Methods Forty Chinese healthy volunteers were divided into three groups according to the PCR-RFLP: CYP2B6 * 1 / * 1 group (n = 29), CYP2B6 * 1 / * 6 (n = 8) and CYP2B6 * 6 / * 6 groups (n = 3). Subjects received a single oral dose of efavirenz 600 mg. A series of blood samples were collected within 336 h after administration. The plasma concentrations of efavirenz were determined by HPLC-MS / MS and the pharmacokinetics were analyzed. Results Compared with CYP2B6 * 1 / * 1 group, the plasma levels of efavirenz of CYP2B6 * 6 / * 6 genotype were higher (P <0.05); CYP2B6 * 1 / * 6 group and CYP2B6 * 6 / * The main pharmacokinetic parameters (t1 / 2, AUC0-336 h and AUC0-∞) of 6 groups were significantly different (P <0.05 or P <0.01); the CYP2B6 * 1 / * 6 group and CYP2B6 * 6 / There was no significant difference between tmax and ρmax in 6 groups (P> 0.05). Conclusion The mutation of CYP2B6 * 6 allele can cause the change of the metabolic phenotype and affect the metabolism of efavirenz in healthy Chinese population. Individualized dosing regimens based on genotypes contribute to the rational use of efavirenz.