Metabolism of Procymidone in Female Rabbits

To examine the metabolic fate of procymidone [N-(3,5-dichlorophenyl)-1,1-dimethylcyclopropane-1,2-dicarboximide, Sumilex®, S-7131], female New Zealand White rabbits were given a single oral dose of [carbonyl- 14 C]procymidone at 125 mg/kg and their urine, feces, and blood were collected. The radiocarbon was rapidly eliminated from the body, the total 14 C excretion within 3 days after administration being 95.3% (urine: 72.1%, and feces: 23.2%). 14 C level in the blood was maintained from 1 -6 hr with a rapid decrease thereafter. The main metabolites in female rabbits were glucuronide conjugates of 3 hydroxylated-procymidone metabolites, which were not found in rats or mice, generated by the following metabolic reactions: 1) oxidation of one of the methyl groups to carboxylic acid via hydroxymethyl, 2) cleavage of the imide linkage, and 3) glucuronide formation of the 3 hydroxylated-procymidone metabolites. The glucuronyltransferase activity toward one of the hydroxylated-procymidone metabolites were examined in vitro with addition of hepatic glucuronyltransferase offemale rabbits or rats. There appeared to be such activity toward hydroxylated-procymidone metabolites only in female rabbits and no activity in female rats, suggesting the difference of the conjugation activity caused the species difference of procymidone metabolism between female rabbits and rats.