Effects of two pulmonary tuberculosis drug treatments and acetylator status on liver function in a Zimbabwean population.
In Zimbabwe patients with pulmonary tuberculosis who are acid-fast bacilli (AFB) negative in the sputum are treated in the two month intensive phase with isoniazid, thiacetazone pyrazinamide and streptomycin (regimen A). Sputum positive patients receive regimen A plus rifampicin (regimen B). Both groups continue treatment with isoniazid and thiacetazone. 21 patients on regimen A and 19 on regimen B had clinical assessment and liver function tests performed at weeks 0, 2, 4, 8, and 12 weeks of treatment (during and four weeks after, the intensive phase of 8 weeks). Acetylator status was also assessed, no significant difference was found between patients on regimen A or B (41 per cent and 45 per cent fast acetylators respectively). Liver function tests results (alanine aminotransferase and alkaline phosphatase) showed a persisting rise during the intensive phase on both regimens, and further rise after four weeks in the continuation phase, this further rise reaching statistical significance in regimen B. These results are unexpected when compared to other studies but the regimens under investigation are not used elsewhere. The significant rise after stopping intensive therapy in regimen B suggests some protective effect of rifampicin against the hepatotoxicity of the regimen, possibly the isoniazid/thiacetazone component. Acetylator status did not influence the degree of hepatotoxicity.
Neill
P
P
Department of Clinical Pharmacology, University of Zimbabwe, School of Medicine, Harare.
Pringle
D
D
Mhonda
M
M
Kusema
T
T
Nhachi
C F
CF
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood* / Q000209:etiology; D004359:Drug Therapy, Combination; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011718:Pyrazinamide / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012293:Rifampin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D013307:Streptomycin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*; D015030:Zimbabwe
D011718:Pyrazinamide; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D007538:Isoniazid; D012293:Rifampin; D013307:Streptomycin