Singkham Noppaket, Avihingsanon Anchalee, Brundage Richard C, Birnbaum Angela K, Thammajaruk Narukjaporn, Ruxrungtham Kiat, Bunupuradah Torsak, Kiertiburanakul Sasisopin, Chetchotisakd Ploenchan, Punyawudho Baralee
Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand.
School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand.
Expert Rev Clin Pharmacol. 2022 Jan;15(1):99-108. doi: 10.1080/17512433.2022.2000858. Epub 2021 Nov 26.
This population pharmacokinetic-pharmacogenetic study aimed to investigate the optimal dose of RTV-boosted ATV (ATV/RTV) for Thai adult HIV-infected patients.
A total of 1460 concentrations of ATV and RTV from 544 patients receiving an ATV/RTV-based regimen were analyzed. The 6986 A > G, 3435 C > T, 2677 G > T, 521 T > C, and 63396 C > T were genotyped. A population pharmacokinetic model was performed using a nonlinear mixed-effect model (NONMEM®). Monte Carlo simulations were conducted to compare the percentages of patients achieving the therapeutic range of ATV through concentrations (C).
The apparent oral clearance of ATV (CL/F) without RTV was 7.69 L/h with interindividual variability (IIV) of 28.7%. Patients with 6986 GG had a 7.1% lower CL/F than those with AA or AG genotype. The CL/F decreased by 10.8% for females compared with males. Simulation results showed higher percentages (70%) of patient receiving doses of 200/100 or 200/50 mg achieved the target ATV C, while more patients (40%) receiving a standard dose (300/100 mg) had ATV C above this target.
Both 6986 A > G and female decreased CL/F in Thai HIV-infected patients. Simulations supported that the reduced dose of ATV/RTV was sufficient to achieve the target concentration for Thai population.
这项群体药代动力学-药物遗传学研究旨在调查洛匹那韦增强的阿扎那韦（ATV/RTV）在泰国成年HIV感染患者中的最佳剂量。
分析了544例接受基于ATV/RTV方案治疗的患者的1460份阿扎那韦和洛匹那韦血药浓度。对6986A>G、3435C>T、2677G>T、521T>C和63396C>T进行基因分型。使用非线性混合效应模型（NONMEM®）建立群体药代动力学模型。进行蒙特卡洛模拟，以比较通过血药浓度（C）达到阿扎那韦治疗范围的患者百分比。
无洛匹那韦时阿扎那韦的表观口服清除率（CL/F）为7.69L/h，个体间变异（IIV）为28.7%。6986GG基因型患者的CL/F比AA或AG基因型患者低7.1%。女性的CL/F比男性降低了10.8%。模拟结果显示，接受200/100或200/50mg剂量的患者达到阿扎那韦目标血药浓度C的百分比更高（约70%），而接受标准剂量（300/100mg）的患者中，有更多患者（约40%）的阿扎那韦血药浓度C高于该目标值。
在泰国HIV感染患者中，6986A>G和女性均降低了阿扎那韦的CL/F。模拟结果支持，降低ATV/RTV剂量足以使泰国人群达到目标血药浓度。
