TY - JOUR T1 - Studies on the effects of isoniazid on acetylhydrazine metabolism in vivo and in vitro. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 237 LP - 240 VL - 7 IS - 4 AU - J A Timbrell AU - J M Wright Y1 - 1979/07/01 UR - http://dmd.aspetjournals.org/content/7/4/237.abstract N2 - 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. ER -