Format

Send to

Choose Destination
Pharmacogenomics. 2017 Nov;18(16):1481-1490. doi: 10.2217/pgs-2017-0128. Epub 2017 Oct 24.

Pharmacogenetics-based population pharmacokinetic analysis of tenofovir in Thai HIV-infected patients.

Author information

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.

KEYWORDS:

ABCC2; ABCC4; Thai HIV-infected patients; population pharmacokinetics; tenofovir

PMID:
29061086
DOI:
10.2217/pgs-2017-0128
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center