Monoacetylhydrazine as a metabolite of isoniazid in man

The potent hepatotoxin, acetylhydrazine (monoacetylhydrazine), has been identified by gas chromatography-mass spectrometry as a urinary metabolite of isoniazid in man. Using a specific gas chromatographic assay procedure for acetylhydrazine, the urinary excretion of this metabolite in volunteers given a 300-mg dose of isoniazid was found to be 1.8 +/- 0.4% and 2.5 +/- 0.5% of the dose in the rapid and slow acetylators, respectively. In the same subjects the urinary excretion of diacetylhydrazine was significantly greater in the rapid acetylators, 23.0 +/- 2.0%, than in the slow acetylators, 4.9 +/- 0.9%. The results suggests that only part of the acetylhydrazine formed as a metabolite of isoniazid is excreted in the urine as acetylhydrazine and diacetylhydrazine and that a substantial proportion of the acetylhydrazine formed is further metabolized, possibly through the microsomal enzyme pathway known to be responsible for hepatotoxicity in experimental animals.