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DOI: https://doi.org/10.4046/trd.2020.0068    [Accepted]
Published online November 3, 2020.
The Influence of NAT2 Genotypes on Isoniazid Plasma Concentration of Pulmonary Tuberculosis Patients in Southern Thailand
U. Ungcharoen, 1, H. Sriplung, 1, S. Mahasirimongkol, 2, S. Chusri, 3, N. Wichukchinda, 2, P. Mokmued, 2, S. Wattanapokayakit, 2, V. Chongsuvivatwong, 1
1Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
2Division of Genomic Medicine and Innovation Support, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand
3Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
Correspondence:  H. Sriplung, Tel: +66-74-451165, 
Email: hutcha.s@psu.ac.th
Received: 2 July 2020   • Revised: 5 October 2020   • Accepted: 3 November 2020
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 TB patients and correlate their genotype with plasma isoniazid concentrations.
Methods
Blood samples from 55 newly diagnosed pulmonary tuberculosis participants from 3 hospitals were collected to classify the subject by NAT2 genotype performed by the Multiplex Haplotype-Specific PCR method. Patients were grouped into three acetylators (fast, intermediate, and slow). On day 14 of TB treatment, the second blood sample was taken to estimate the peak plasma concentration at two hours after oral administration. INH plasma concentration was analyzed by liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-Ms/Ms) method.
Results
The NAT2 genotype distribution of fast, intermediate, and slow acetylator was 10.9%, 36.4%, and 52.7%, from 6, 20, 29 patients, respectively. The median (IQR) of INH plasma concentration at two 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, 5.5) µg/mL, from 4, 14, 12 cases, respectively. The INH plasma concentration at two hours after administration was significantly associated with body weight and NAT2 acetylator.
Conclusions
The INH plasma concentration was found lower in fast than intermediate and slow acetylators. Body weight and NAT2 acetylator influenced INH plasma concentrations at two hours after drug administration. Therefore, the NAT2 genotype should be known before starting TB treatment to maximize therapeutic outcomes.
Key Words: Isoniazid, NAT2 genotype, N-acetyltransferase 2, Plasma concentration, Tuberculosis


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