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The Influence of NAT2 Genotypes on Isoniazid Plasma Concentration of Pulmonary Tuberculosis Patients in Southern Thailand

Tuberculosis and Respiratory Diseases 2020년 83권 0호 p.55 ~ 62
Ungcharoen Usanee, Sriplung Hutcha, Mahasirimongkol Surakameth, Chusri Saranyou, Wichukchinda Nuanjun, Mokmued Phongpan, Wattanapokayakit Sukanya, Chongsuvivatwong Virasakdi,
소속 상세정보
 ( Ungcharoen Usanee ) - Prince of Songkla University Faculty of Medicine Epidemiology Unit
 ( Sriplung Hutcha ) - Prince of Songkla University Faculty of Medicine Epidemiology Unit
 ( Mahasirimongkol Surakameth ) - Ministry of Public Health Department of Medical Sciences
 ( Chusri Saranyou ) - Prince of Songkla University Faculty of Medicine Department of Internal Medicine
 ( Wichukchinda Nuanjun ) - Ministry of Public Health Department of Medical Sciences
 ( Mokmued Phongpan ) - Ministry of Public Health Department of Medical Sciences
 ( Wattanapokayakit Sukanya ) - Ministry of Public Health Department of Medical Sciences
 ( Chongsuvivatwong Virasakdi ) - Prince of Songkla University Faculty of Medicine Epidemiology Unit

Abstract


Background: Isoniazid (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.

Methods: Blood 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.

Results: The 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.

Conclusion: The 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.

키워드

Isoniazid; NAT2 Genotype; N-acetyltransferase 2; Plasma Concentration; Tuberculosis

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