Pharmacogenetics-based population pharmacokinetic analysis of tenofovir in Thai HIV-infected patients
SourcePharmacogenomics, 18, 16, (2017), pp. 1481-1490
Article / Letter to editor
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SubjectRadboudumc 4: lnfectious Diseases and Global Health RIHS: Radboud Institute for Health Sciences
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.
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