Effect of hepatic microsomal enzyme inducers on the metabolism of misonidazole in rats.
Pretreatment of rats with the hepatic microsomal enzyme inducers, phenobarbital or phenytoin, increased the metabolism of the hypoxic cell radiosensitizer, misonidazole. The increase was reflected in the ratio of O-demethylated metabolite to unchanged drug in the 24-hour urine collection and was more extensive with phenobarbital. No inducement was observed after pretreatment with dexamethasone or misonidazole. Such pretreatment with inducers prior to misonidazole therapy would be clinically important since the incidence of neurotoxicity may be reduced without impairment of the radiosensitizing effect.
D000818:Animals; D005243:Feces / Q000032:analysis; D007274:Injections, Intraperitoneal; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D008920:Misonidazole / Q000378:metabolism*; D009593:Nitroimidazoles / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology* / Q000652:urine; D010672:Phenytoin / Q000494:pharmacology* / Q000652:urine; D051381:Rats; D013997:Time Factors
D009593:Nitroimidazoles; D010672:Phenytoin; D008920:Misonidazole; D010634:Phenobarbital