J Korean Med Sci.  2015 Feb;30(2):167-172. 10.3346/jkms.2015.30.2.167.

Drug-induced Hepatotoxicity of Anti-tuberculosis Drugs and Their Serum Levels

Affiliations
  • 1Department of Internal Medicine, National Medical Center, Seoul, Korea.
  • 2Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. jhlee7@snubh.org
  • 3Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

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.

Keyword

Therapeutic Drug Monitoring; Hepatotoxicity; Tuberculosis

MeSH Terms

Adolescent
Adult
Aged
Aged, 80 and over
Alanine Transaminase/blood
Antitubercular Agents/adverse effects/*blood/therapeutic use
Aspartate Aminotransferases/blood
Drug-Induced Liver Injury/*blood
Ethambutol/adverse effects/blood/therapeutic use
Female
Humans
Isoniazid/adverse effects/blood/therapeutic use
Liver/*pathology
Liver Function Tests
Male
Middle Aged
Pyrazinamide/adverse effects/blood/therapeutic use
Retrospective Studies
Rifampin/adverse effects/blood/therapeutic use
Tuberculosis, Pulmonary/drug therapy
Young Adult
Antitubercular Agents
Aspartate Aminotransferases
Alanine Transaminase
Ethambutol
Isoniazid
Pyrazinamide
Rifampin

Figure

  • Fig. 1 Flow diagram showing the progress of study subjects through the study. TDM, therapeutic drug monitoring; TB, tuberculosis; DIH, drug induced hepatotoxicity.


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