Studies in detoxication. 77. The metabolism of phenylhydrazine and some phenylhydrazones

Abstract

(C14) Phenylhydrazine hydrochloride administered orally to rabbits in doses of 50 mg/kg is slowly metabolized. In 4 days 50% of the dose is excreted in the urine, the rest being found in the body, particularly the erythrocytes (10%). There is a slow excretion of radioactivity for at least 10 days after dosing, and in this time the excreted radioactivity accounts for about 60% of the dose. The principal urinary metabolites have been identified as p-hydrazinophenol (17%), probably present as the glucuronide, pyruvic acid phenylhydrazone (8.5%) and a-oxoglutaric acid phenylhydrazone (5.2%). Traces of the phenylhydrazones of acetone, pyridoxal and acetoacetic acid may also be present in the urine. The phenylhydrazones of pyruvic acid and a-oxoglutaric acid are less toxic than phenylhydrazine and when administered are quickly excreted. When pyruvic acid (Cl4) phenylhydrazone is injected, it is excreted in the urine largely as such (93%) but partly as a-oxoglutaric acid phenylhydrazone (7%). When administered orally it is hydrolyzed in the gut and excreted in the urine as conjugated p-hydroxyphenyldydrazine (33%) together with the phenylhydrazones of pyruvic acid (31%) and a-oxoglutaric acid (5%). Similar results were obtained with a-oxoglutaric acid (Cl4) phenylhydrazone. Acetyl (Cl4) phenylhydrazine, when administered orally to rabbits, is slowly excreted as metabolites and in 2 days about 29% of the dose is found in the urine as conjugated p-hydroxyphenylhydrazine (14%), unchanged acetylphenylhydrazine (4.7%) and pyruvic acid phenylhydrazone (1.4%).