ArticleTuberculosis and respiratory diseases2020
The Influence of NAT2 Genotypes on Isoniazid Plasma Concentration of Pulmonary Tuberculosis Patients in Southern Thailand.
Article in Tuberculosis and respiratory diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.
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2 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.
- Efficacy, safety, and pharmacokinetics of isoniazid affected by NAT2 polymorphisms in patients with tuberculosis: A systematic review.Clinical and translational science · 2024Pooled it
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8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIsoniazid (INH) is metabolized by polymorphic N-acetyltransferase 2 (NAT2) enzyme, which noticeably alters INH plasma concentration. We aimed to determine the distribution of NAT2 genotype in Thai tuberculosis (TB) patients and correlate their genotype with plasma INH concentrations.
methodsBlood samples from 55 newly diagnosed pulmonary tuberculosis participants from three hospitals were collected to classify the subject by NAT2 genotype performed by the Multiplex haplotype-specific polymerase chain reaction method. Patients were grouped into three acetylators (fast, intermediate, and slow). On day 14 of tuberculosis treatment, the second blood sample was taken to estimate the peak plasma concentration at 2 hours after oral administration. INH plasma concentration was analyzed by liquid chromatography‒tandem mass spectrometry/mass spectrometry method.
resultsThe NAT2 genotype distribution of fast, intermediate, and slow acetylator was 10.9%, 36.4%, and 52.7%, from six, 20, and 29 patients, respectively. The median (interquartile range) of INH plasma concentration at 2 hours post drug administration for these three genotypes were 0.75 (0.69-0.86), 2.56 (2.12-3.97), and 4.25 (3.56-5.50) µg/mL from four, 14, and 12 cases, respectively. The INH plasma concentration at 2 hours after administration was significantly associated with body weight and NAT2 acetylator.
conclusionThe INH plasma concentration was found lower in fast than intermediate and slow acetylators. Body weight and NAT2 acetylator influenced INH plasma concentrations at 2 hours after drug administration. Therefore, the NAT2 genotype should be known before starting TB treatment to maximize therapeutic outcomes.
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