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Metabolism of 14C-iodochlorhydroxyquin in the dog and the rat.

The disposition and metabolism of iodochlorhydroxyquin (clioquinol), an amebicidal drug with neurotoxic properties, were studied in dogs and rats with 14C-labelled drug. Pharmacokinetic studies in the dog demonstrated that the compound was well absorbed; the bioavailability was 36% of the dose of 1 mg/kg. The serum half-life was 1.3-1.8 h. In both the dog and the rat, biliary excretion was a major route of elimination. The dog excreted 27% of an intravenously administered dose (1 mg/kg) in the bile within 2 h; the rat excreted 39% of the dose (5 mg/kg i.v.) in less than 3 h. Elimination via the renal route was also substantial in both species. Urinary and biliary metabolites were separated by TLC (thin layer chromatography) and identified as sulfate and glucuronide conjugates in both species. No evidence for any other metabolites was found. A significant difference was observed between the dog and the rat in the extent of conjugation; the percentage radioactivity in the urine accounted for by the unchanged compound was six to twenty times greater for the dog than for the rat. The species differences in the disposition and metabolism of the compound might explain its greater toxicity in the dog than in the rat.