基于药物遗传学的泰国HIV感染患者中替诺福韦的群体药代动力学分析。
Pharmacogenetics-based population pharmacokinetic analysis of tenofovir in Thai HIV-infected patients.
作者信息
Rungtivasuwan Kanokrat, Avihingsanon Anchalee, Thammajaruk Narukjaporn, Mitruk Siwaporn, Burger David M, Ruxrungtham Kiat, Sukasem Chonlaphat, Punyawudho Baralee
机构信息
Pharmacy Services, Somdech Phra Debaratana Medical Center, Ramathibodi Hospital, Bangkok, Thailand.
HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
出版信息
Pharmacogenomics. 2017 Nov;18(16):1481-1490. doi: 10.2217/pgs-2017-0128. Epub 2017 Oct 24.
AIM
To develop a population pharmacokinetic model and identify sources of variability, genetic and nongenetic factors, of tenofovir.
METHODS
The ABCC2 and ABCC4 polymorphisms were genotyped in 342 patients. A nonlinear mixed effects model was used to develop the population pharmacokinetic model and investigate the influence of these polymorphisms and other patient specific covariates on the pharmacokinetics of tenofovir.
RESULTS
The estimated glomerular filtration rate calculated by the Cockcroft and Gault equation, concomitant use of lopinavir/ritonavir and ABCC4 3463A>G polymorphism were associated with tenofovir apparent oral clearance (CL/F). The use of lopinavir/ritonavir decreased tenofovir CL/F by 25%. Patients carrying ABCC4 3463 AG or GG had a tenofovir CL/F 11% higher than those with genotype AA.
CONCLUSION
Renal function, co-medication and genetic variation impact the pharmacokinetics of tenofovir. These factors should be taken into consideration to guide the individual tenofovir disoproxil fumarate dosage regimen in Thai HIV-infected patients.
目的
建立替诺福韦的群体药代动力学模型，并确定其变异性来源，包括遗传和非遗传因素。
方法
对342例患者进行ABCC2和ABCC4基因多态性基因分型。采用非线性混合效应模型建立群体药代动力学模型，并研究这些多态性和其他患者特异性协变量对替诺福韦药代动力学的影响。
结果
通过Cockcroft和Gault方程计算的估计肾小球滤过率、洛匹那韦/利托那韦的联合使用以及ABCC4 3463A>G多态性与替诺福韦的表观口服清除率（CL/F）相关。洛匹那韦/利托那韦的使用使替诺福韦的CL/F降低了25%。携带ABCC4 3463 AG或GG基因型的患者的替诺福韦CL/F比基因型AA的患者高11%。
结论
肾功能、联合用药和基因变异会影响替诺福韦的药代动力学。在指导泰国HIV感染患者的替诺福韦酯个体化给药方案时，应考虑这些因素。
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