The Influence of NAT2 Genotypes on Isoniazid Plasma Concentration of Pulmonary Tuberculosis Patients in Southern Thailand
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. Meth...
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| Format: | Article |
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The Korean Academy of Tuberculosis and Respiratory Diseases
2020-12-01
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| Series: | Tuberculosis and Respiratory Diseases |
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| Online Access: | http://www.e-trd.org/upload/pdf/trd-2020-0068.pdf |
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| author | Usanee Ungcharoen Hutcha Sriplung Surakameth Mahasirimongkol Saranyou Chusri Nuanjun Wichukchinda Phongpan Mokmued Sukanya Wattanapokayakit Virasakdi Chongsuvivatwong |
| author_facet | Usanee Ungcharoen Hutcha Sriplung Surakameth Mahasirimongkol Saranyou Chusri Nuanjun Wichukchinda Phongpan Mokmued Sukanya Wattanapokayakit Virasakdi Chongsuvivatwong |
| author_sort | Usanee Ungcharoen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T07:51:59Z |
| format | Article |
| id | doaj.art-f696a40629924235b2b42fc46a9e1601 |
| institution | Directory Open Access Journal |
| issn | 1738-3536 2005-6184 |
| language | English |
| last_indexed | 2024-12-20T07:51:59Z |
| publishDate | 2020-12-01 |
| publisher | The Korean Academy of Tuberculosis and Respiratory Diseases |
| record_format | Article |
| series | Tuberculosis and Respiratory Diseases |
| spelling | doaj.art-f696a40629924235b2b42fc46a9e16012022-12-21T19:47:48ZengThe Korean Academy of Tuberculosis and Respiratory DiseasesTuberculosis and Respiratory Diseases1738-35362005-61842020-12-0183Supple 1S55S6210.4046/trd.2020.00683296The Influence of NAT2 Genotypes on Isoniazid Plasma Concentration of Pulmonary Tuberculosis Patients in Southern ThailandUsanee Ungcharoen0Hutcha Sriplung1Surakameth Mahasirimongkol2Saranyou Chusri3Nuanjun Wichukchinda4Phongpan Mokmued5Sukanya Wattanapokayakit6Virasakdi Chongsuvivatwong7 Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand Division of Genomic Medicine and Innovation Support, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand Division of Genomic Medicine and Innovation Support, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand Division of Genomic Medicine and Innovation Support, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand Division of Genomic Medicine and Innovation Support, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, Hat Yai, ThailandBackground 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.http://www.e-trd.org/upload/pdf/trd-2020-0068.pdfisoniazid genotypen-acetyltransferase 2plasma concentrationtuberculosis |
| spellingShingle | Usanee Ungcharoen Hutcha Sriplung Surakameth Mahasirimongkol Saranyou Chusri Nuanjun Wichukchinda Phongpan Mokmued Sukanya Wattanapokayakit Virasakdi Chongsuvivatwong The Influence of NAT2 Genotypes on Isoniazid Plasma Concentration of Pulmonary Tuberculosis Patients in Southern Thailand Tuberculosis and Respiratory Diseases isoniazid genotype n-acetyltransferase 2 plasma concentration tuberculosis |
| title | The Influence of NAT2 Genotypes on Isoniazid Plasma Concentration of Pulmonary Tuberculosis Patients in Southern Thailand |
| title_full | The Influence of NAT2 Genotypes on Isoniazid Plasma Concentration of Pulmonary Tuberculosis Patients in Southern Thailand |
| title_fullStr | The Influence of NAT2 Genotypes on Isoniazid Plasma Concentration of Pulmonary Tuberculosis Patients in Southern Thailand |
| title_full_unstemmed | The Influence of NAT2 Genotypes on Isoniazid Plasma Concentration of Pulmonary Tuberculosis Patients in Southern Thailand |
| title_short | The Influence of NAT2 Genotypes on Isoniazid Plasma Concentration of Pulmonary Tuberculosis Patients in Southern Thailand |
| title_sort | influence of nat2 genotypes on isoniazid plasma concentration of pulmonary tuberculosis patients in southern thailand |
| topic | isoniazid genotype n-acetyltransferase 2 plasma concentration tuberculosis |
| url | http://www.e-trd.org/upload/pdf/trd-2020-0068.pdf |
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