Renal elimination of the hypoxic cell radiosensitizer misonidazole in Wistar rats: influence of some drugs on its excretion.
The hypoxic cell radiosensitizing drug, misonidazole (Miso) (Ro 07-0582) and its demethylated metabolite were administered to Wistar rats at different dose levels to examine their renal elimination. The data were consistent with a model in which Miso is eliminated mainly after biotransformation into desmethylmisonidazole (Demiso) which is eliminated according to its renal clearance. The study of Miso renal elimination process shows a tubular reabsorption. So we analyzed the interaction of various drugs on urinary 24 hours elimination of this radiosensitizer. Following results were observed: Furosemide and acetazolamide do not change the rate of renal elimination of the drug; Soludactone increases the elimination level of unmetabolized Miso (p less than 0.01); Under probenecid treatment, the elimination of Miso and its O-demethylated derivative are increased; On the other hand, after a pretreatment with phenobarbital, the urinary level of desmethylmisonidazole is strongly increased (p less than 0.001).
D000818:Animals; D003640:Dealkylation; D004232:Diuretics / Q000494:pharmacology; D004347:Drug Interactions; D005965:Glucuronates / Q000652:urine; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008920:Misonidazole / Q000652:urine*; D010634:Phenobarbital / Q000494:pharmacology; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D004232:Diuretics; D005965:Glucuronates; D008920:Misonidazole; D011339:Probenecid; D010634:Phenobarbital