[Incidence of hepatotoxic side effects during antituberculous therapy (INH, RMP, EMB) in relation to the acetylator phenotype (author's transl)].
In 95 patients with active tuberculosis, we investigated in a prospective study the influence of the acetylator phenotype on the hepatotoxic side effects of the antituberculous regimen isoniazid (INH) 10 mg/kg, rifampicin (RMP) 10 mg/kg, and ethambutol (EMB) 25 mg/kg. Besides a much higher incidence of isoniazid hepatitis (SGOT, SGPT greater than 200 U/l) in 12.6% of patients treated--as compared to the incidence reported in large chemoprophylaxis trials with isoniazid monotherapy in the range of 0.5%-1% (IUAT 1969, U.S.P.H.S. 1971)--we observed a significant, higher risk of isoniazid-induced hepatotoxicity in slow acetylators (p less than 0.01): in 26 of 56 slow acetylators (= 46.4%), but only in 4 of 30 rapid acetylators (=13.3%) were transaminases in the serum elevated greater than 50 U/l. The 12 patients with the most severe hepatotoxic side effects (SGOT, SGPT greater than 200 U/l) were all slow acetylators. Women developed severe hepatic injury more often than men (p less than 0.05). In cases with isoniazid hepatitis, triple therapy was either stopped or reduced to a combination RMP, EMB. In cases with less severe liver injury, triple therapy was continued. In all patients transaminases normalized within 2-4 weeks. On return to full triple therapy, none of the patients developed new elevation of transaminases. The constant occurrence of isoniazid hepatitis during the 2nd-4th week (19 +/- 7 days) as well as the normalization without any new hepatotoxic reaction suggest that there may be an interaction between RMP and isoniazid metabolism limited to the early phase of chemotherapy.
D000107:Acetylation; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics*; D004977:Ethambutol / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects* / Q000627:therapeutic use; D010641:Phenotype; D012293:Rifampin / Q000009:adverse effects* / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy
D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin
Die Häufigkeit hepatotoxischer Nebenwirkungen der tuberkulostatischen Kombinationstherapie (INH, RMP, EMB) in Abhängigkeit vom Acetyliererphänotyp.