Pharmacogenetics-based population pharmacokinetic analysis for dose optimization of ritonavir-boosted atazanavir in Thai adult HIV-infected patients
| العنوان: | Pharmacogenetics-based population pharmacokinetic analysis for dose optimization of ritonavir-boosted atazanavir in Thai adult HIV-infected patients |
|---|---|
| المؤلفون: | Sasisopin Kiertiburanakul, Ploenchan Chetchotisakd, Kiat Ruxrungtham, Lasa study team, Noppaket Singkham, Torsak Bunupuradah, Baralee Punyawudho, Angela K. Birnbaum, Anchalee Avihingsanon, Richard C. Brundage, Narukjaporn Thammajaruk |
| المصدر: | Expert Review of Clinical Pharmacology. 15:99-108 |
| بيانات النشر: | Informa UK Limited, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, medicine.medical_specialty, Anti-HIV Agents, Atazanavir Sulfate, Population, HIV Infections, Gastroenterology, Therapeutic index, Pharmacokinetics, Internal medicine, Humans, Medicine, Pharmacology (medical), General Pharmacology, Toxicology and Pharmaceutics, education, education.field_of_study, Ritonavir, biology, Liver-Specific Organic Anion Transporter 1, business.industry, General Medicine, Thailand, Atazanavir, Regimen, Pharmacogenetics, biology.protein, Female, business, SLCO1B1, human activities, medicine.drug |
| الوصف: | BACKGROUND 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. |
| تدمد: | 1751-2441 1751-2433 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0561898ee41be059a65ea45fee7c7af5Test https://doi.org/10.1080/17512433.2022.2000858Test |
| رقم الانضمام: | edsair.doi.dedup.....0561898ee41be059a65ea45fee7c7af5 |
| قاعدة البيانات: | OpenAIRE |
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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. 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