METABOLISM OF PROCYMIDONE IN FEMALE RABBITS

To examine the metabolic fate of procymidone henyl)-1,2-dimethylcyclop ropane-1,2-dicarboximide, Sumilex(R), S-7131], female New Zealand Whit e rabbits were given a single oral dose of [carbonyl-C-14] procymidone at 125 mg/kg and their urine, feces, and blood were collected. The ra diocarbon was rapidly eliminated from the body, the total C-14 excreti on within 3 days after administration being 95.3% (urine: 72.1%; and f eces: 23.2%). C-14 level in the blood was maintained from 1-6 hr with a rapid decrease thereafter. The main metabolites in female rabbits we re glucuronide conjugates of 3 hydroxylated-procymidone metabolites, w hich were not found in rats or mice, generated by the following metabo lic reactions: 1) oxidation of one of the methyl groups to carboxylic acid via hydroxymethyl, 2) cleavage of the imide linkage, and 3) glucu ronide formation of the 3 hydroxylated-procymidone metabolites. The gl ucuronyltransferase activity toward one of the hydroxylated-procymidon e metabolites were examined in vitro with addition of hepatic glucuron yltransferase of female rabbits or rats. There appeared to be such act ivity toward hydroxylated-procymidone metabolites only in female rabbi ts and no activity in female rats, suggesting the difference of the co njugation activity caused the species difference of procymidone metabo lism between female rabbits and rats.