The pharmacokinetics of misonidazole in the dog

The hypoxic cell radiosensitising drug misonidazole, [1-(2-nitroimidazol-1-yl)-3-methoxypropan-2-ol, Ro 07-0582] was administered to dogs at dose levels of 50-200 mg/kg on four consecutive weekly occasions by oral and intravenous routes. High-performance liquid chromatography was used to monitor the subsequent plasma concentrations of misonidazole and its 0-demethylated metabolite [1-(2-nitroimidazol-1-yl)-2,3-propandiol, Ro 05-9963]. Both misonidazole and Ro 05-9963 were also detected in the urine in the free and glucuronide-conjugated forms. The detailed pharmacokinetics of misonidazole in the dog are presented and some observations are made on the toxicity of the drug in this species. We conclude in the light of these pharmacokinetic data that the dog may prove to be a better model for the study of misonidazole than those presently used in the laboratory, particularly the rodent species.