Effects of genetic variability on rifampicin and isoniazid pharmacokinetics in South African patients with recurrent tuberculosis
| Autor: | Maxwell Chirehwa, Katya Govender, Kogieleum Naidoo, Sinaye Ncgapu, Paolo Denti, Ravesh Singh, John W. Adamson, Nonhlanhla Yende-Zuma, Helen McIlleron, Nesri Padayatchi, Anushka Naidoo, Veron Ramsuran |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male ATP Binding Cassette Transporter Subfamily B Tuberculosis Genotype Arylamine N-Acetyltransferase Pharmacology Polymorphism Single Nucleotide 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Recurrence Isoniazid Genetics Humans Medicine Genetic variability Glucuronosyltransferase biology Liver-Specific Organic Anion Transporter 1 business.industry Pyrazinamide medicine.disease 030220 oncology & carcinogenesis biology.protein Molecular Medicine Female Rifampin business SLCO1B1 Pharmacogenetics Rifampicin Research Article medicine.drug |
| Zdroj: | Pharmacogenomics. 20:225-240 |
| ISSN: | 1744-8042 1462-2416 |
| DOI: | 10.2217/pgs-2018-0166 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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