The metabolic fate of 3[H]econazole in man

1. Following single oral doses of 3[H]econazole base (500 mg) to two human subjects, excretion of radioactivity was prolonged, and incomplete after five days (means of 40% and 27% dose in urine and faeces respectively). 2. Plasma concn. of unchanged econazole and total radioactivity attained peak values at approx. the same for each subject (1.5 - 3h), but the former declined much faster than the latter. Most of the 3H in early plasma samples was present as unchanged drug and extractable metabolites, but after 24h concn. of econazole were close to the limit of detection (0.04 ug/ml) and very little plasma 3H was extractable, whereas total 3H concn. were still measurable after five days (mean 1.54 ug/ml). Thus, plasma contained metabolites with much longer half-lives than econazole. 3. The main route of biotransformation of econazole in man involved multiple oxidation of the imidazole ring carbons followed by O-dealkylation and conjugation of the resulting alcohols, probably with glucuronic acid.