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Title: Pharmacogenetics-based population pharmacokinetic analysis of tenofovir in Thai HIV-infected patients
Authors: Kanokrat Rungtivasuwan
Anchalee Avihingsanon
Narukjaporn Thammajaruk
Siwaporn Mitruk
David M. Burger
Kiat Ruxrungtham
Chonlaphat Sukasem
Baralee Punyawudho
Faculty of Medicine, Ramathibodi Hospital, Mahidol University
The HIV Netherlands Australia Thailand Research Collaboration
Chulalongkorn University
Vajira Hospital
Radboud University Nijmegen Medical Centre
Mahidol University
Chiang Mai University
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Nov-2017
Citation: Pharmacogenomics. Vol.18, No.16 (2017), 1481-1490
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.
ISSN: 17448042
Appears in Collections:Scopus 2016-2017

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