Kanokrat Rungtivasuwan1, Anchalee Avihingsanon2,3, Narukjaporn Thammajaruk2, Siwaporn Mitruk4, David M Burger5, Kiat Ruxrungtham2,3, Chonlaphat Sukasem6,7, Baralee Punyawudho8. 1. Pharmacy Services, Somdech Phra Debaratana Medical Center, Ramathibodi Hospital, Bangkok, Thailand. 2. HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand. 3. Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 4. Department of Pharmacy, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand. 5. Department of Pharmacy, Radbound University Medical Center, Nijmegen, The Netherlands. 6. Division of Pharmacogenomics & Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. 7. Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bankok, Thailand. 8. Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand.
Abstract
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.
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-infectedpatients.
Entities:
Keywords:
ABCC2; ABCC4; Thai HIV-infected patients; population pharmacokinetics; tenofovir
Authors: Eric H Decloedt; Phumla Z Sinxadi; Lubbe Wiesner; John A Joska; David W Haas; Gary Maartens Journal: South Afr J HIV Med Date: 2021-04-28 Impact factor: 2.744