Studies on the effects of isoniazid on acetylhydrazine metabolism in vivo and in vitro.

The interaction of isoniazid with its hepatotoxic metabolite acetylhydrazine has been studied. In vitro, isoniazid at a concentration of 0.5 mM was found to inhibit the microsomal metabolism of acetylhydrazine to a reactive acylating species. In vivo, however, coadministered isoniazid inhibited the acetylation to diacetylhydrazine and concomitantly increased the microsomal metabolism of 14C-acetylhydrazine to a reactive intermediate which covalently bound to liver macromolecules. Comparison of urinary metabolites of isoniazid at two dose levels indicated that acetylation of acetylhydrazine produced as a metabolite may be inhibited by the parent drug.