Singkham N.Avihingsanon A.Brundage R.C.Birnbaum A.K.Thammajaruk N.Ruxrungtham K.Bunupuradah T.Kiertiburanakul S.Chetchotisakd P.Punyawudho B.Mahidol University2023-06-182023-06-182022-01-01Expert Review of Clinical Pharmacology Vol.15 No.1 (2022) , 99-10817512433https://repository.li.mahidol.ac.th/handle/20.500.14594/86729Background: This population pharmacokinetic–pharmacogenetic study aimed to investigate the optimal dose of RTV-boosted ATV (ATV/RTV) for Thai adult HIV-infected patients. Methods: A total of 1460 concentrations of ATV and RTV from 544 patients receiving an ATV/RTV-based regimen were analyzed. The CYP3A5 6986 A > G, ABCB1 3435 C > T, ABCB1 2677 G > T, SLCO1B1 521 T > C, and NR1I2 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 (Ctrough). Results: The apparent oral clearance of ATV (CL/FATV) without RTV was 7.69 L/h with interindividual variability (IIV) of 28.7%. Patients with CYP3A5 6986 GG had a 7.1% lower CL/FATV than those with AA or AG genotype. The CL/FATV 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 Ctrough, while more patients (~40%) receiving a standard dose (300/100 mg) had ATV Ctrough above this target. Conclusions: Both CYP3A5 6986 A > G and female decreased CL/FATV in Thai HIV-infected patients. Simulations supported that the reduced dose of ATV/RTV was sufficient to achieve the target concentration for Thai population.MedicineArticleSCOPUS10.1080/17512433.2022.20008582-s2.0-851200383651751244134727835