Effects of genetic variability on rifampicin and isoniazid pharmacokinetics in South African patients with recurrent tuberculosis
| العنوان: | Effects of genetic variability on rifampicin and isoniazid pharmacokinetics in South African patients with recurrent tuberculosis |
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| المؤلفون: | 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 |
| المصدر: | Pharmacogenomics. 20:225-240 |
| بيانات النشر: | Future Medicine Ltd, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| تدمد: | 1744-8042 1462-2416 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cfef653446ab981495bcfe7cd449f518Test https://doi.org/10.2217/pgs-2018-0166Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....cfef653446ab981495bcfe7cd449f518 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17448042 14622416 |
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