Publication: Pharmacogenetics-based population pharmacokinetic analysis of tenofovir in Thai HIV-infected patients
Issued Date
2017-11-01
Resource Type
ISSN
17448042
14622416
14622416
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2-s2.0-85034419484
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Mahidol University
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SCOPUS
Bibliographic Citation
Pharmacogenomics. Vol.18, No.16 (2017), 1481-1490
Suggested Citation
Kanokrat Rungtivasuwan, Anchalee Avihingsanon, Narukjaporn Thammajaruk, Siwaporn Mitruk, David M. Burger, Kiat Ruxrungtham, Chonlaphat Sukasem, Baralee Punyawudho Pharmacogenetics-based population pharmacokinetic analysis of tenofovir in Thai HIV-infected patients. Pharmacogenomics. Vol.18, No.16 (2017), 1481-1490. doi:10.2217/pgs-2017-0128 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/41724
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Title
Pharmacogenetics-based population pharmacokinetic analysis of tenofovir in Thai HIV-infected patients
Abstract
© 2017 Future Medicine Ltd. 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.