Format

Send to

Choose Destination
Pharmacogenomics. 2019 Mar;20(4):225-240. doi: 10.2217/pgs-2018-0166. Epub 2019 Feb 15.

Effects of genetic variability on rifampicin and isoniazid pharmacokinetics in South African patients with recurrent tuberculosis.

Author information

1
Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa.
2
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
3
KwaZulu-Natal Research Innovation & Sequencing Platform (KRISP), School of Laboratory Medicine & Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
4
MRC-CAPRISA HIV-TB Pathogenesis & Treatment Research Unit, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
5
Department of Microbiology, National Health Laboratory Services, KZN Academic Complex, Inkosi Albert Luthuli Central Hospital, Durban, South Africa.
6
Pharmacology Core, Africa Health Research Institute (AHRI), Durban, South Africa.

Abstract

AIM:

We report the prevalence and effect of genetic variability on pharmacokinetic parameters of isoniazid and rifampicin.

MATERIALS & METHODS:

Genotypes for SLCO1B1, NAT2, PXR, ABCB1 and UGT1A genes were determined using a TaqMan® Genotyping OpenArray™. Nonlinear mixed-effects models were used to describe drug pharmacokinetics.

RESULTS:

Among 172 patients, 18, 43 and 34% were classified as rapid, intermediate and slow NAT2 acetylators, respectively. Of the 58 patients contributing drug concentrations, rapid and intermediate acetylators had 2.3- and 1.6-times faster isoniazid clearance than slow acetylators. No association was observed between rifampicin pharmacokinetics and SLCO1B1, ABCB1, UGT1A or PXR genotypes.

CONCLUSION:

Clinical relevance of the effects of genetic variation on isoniazid concentrations and low first-line tuberculosis drug exposures observed require further investigation.

KEYWORDS:

isoniazid; pharmacogenetics; pharmacokinetics; pyrazinamide; rifampicin; tuberculosis

PMID:
30767706
PMCID:
PMC6562923
[Available on 2020-03-01]
DOI:
10.2217/pgs-2018-0166

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center