title: Drug-induced hepatotoxicity of anti-tuberculosis drugs and their serum levels.
abstract: The correlation between serum anti-tuberculosis (TB) drug levels and the drug-induced hepatotoxicity (DIH) remains unclear. The purpose of this study was to investigate whether anti-TB DIH is associated with basal serum drug levels. Serum peak levels of isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) were analyzed in blood samples 2 hr after the administration of anti-TB medication. Anti-TB DIH and mild liver function test abnormality were diagnosed on the basis of laboratory and clinical criteria. Serum anti-TB drug levels and other clinical factors were compared between the hepatotoxicity and non-hepatotoxicity groups. A total of 195 TB patients were included in the study, and the data were analyzed retrospectively. Seventeen (8.7%) of the 195 patients showed hepatotoxicity, and the mean aspartate aminotransferase/alanine aminotransferase levels in the hepatotoxicity group were 249/249 IU/L, respectively. Among the 17 patients with hepatotoxicity, 12 showed anti-TB DIH. Ten patients showed PZA-related hepatotoxicity and 2 showed INH- or RMP-related hepatotoxicity. However, intergroup differences in the serum levels of the 4 anti-TB drugs were not statistically significant. Basal serum drug concentration was not associated with the risk anti-TB DIH in patients being treated with the currently recommended doses of first-line anti-TB treatment drugs.
authors: Department of Internal Medicine, National Medical Center, Seoul, Korea.
authors: Ina
authors: 0000-0002-0937-9833
authors: I
authors: Jeong
authors: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors: Jong-Sun
authors: 0000-0003-3707-3636
authors: JS
authors: Park
authors: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors: Young-Jae
authors: 0000-0001-6943-4462
authors: YJ
authors: Cho
authors: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors: Ho Il
authors: 0000-0002-5306-3692
authors: HI
authors: Yoon
authors: Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors: Junghan
authors: 0000-0003-0576-9938
authors: J
authors: Song
authors: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors: Choon-Taek
authors: 0000-0001-8030-3332
authors: CT
authors: Lee
authors: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors: Jae-Ho
authors: 0000-0002-4766-1231
authors: JH
authors: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D000995:Antitubercular Agents / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood*; D004977:Ethambutol / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D008099:Liver / Q000473:pathology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011718:Pyrazinamide / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D012189:Retrospective Studies; D012293:Rifampin / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D004977:Ethambutol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D007538:Isoniazid; D012293:Rifampin
keywords: Hepatotoxicity; Therapeutic Drug Monitoring; Tuberculosis
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