Influence of the enterohepatic circulation on the metabolism of chlorphenesin carbamate (CPC). II. Metabolic fate of biliary CPC-glucuronide (author's transl)

Abstract

The metabolic fate of biliary chlorphenesin carbamate (CPC) glucuronide after administration to rats was examined. After intraduodenal administration of the bile containing 14C-CPC glucuronide to bile fistula rats, about 21% of radioactivity administered was excreted into the bile during 48 hr. After intravenous injection of 14C-CPC to intact rats, both the unconjugate and glucuronide were recovered in the intestine and only the unconjugate in portal blood. Hydrolysis of CPC glucuronide by the intestinal content was demonstrated in vivo and in vitro. The rate of disappearance of radioactivity from the looped intestines, to which the glucuronide of 14C-CPC was injected, increased from the jejunum to colon. 14C-CPC was incubated with the everted sacs of rat small intestine at pH 7.4, and a small amount of the hydrolyzed product of CPC, chlorphenesin, was detected in the serosal fluid. Oral administration of synthetic 14C-chlorphenesin to rats and guinea pigs revealed that the compound was converted readily to acidic metabolites of CPC, p-chlorophenoxylactic acid and p-chlorophenoxyacetic acid, in both species. The acidic metabolites of CPC had no muscle relaxant activity. In relation to the urinary excretion of large amount of acidic metabolites in rats, the enterohepatic circulation of CPC and a particularly high activity converting CPC to chlorphenesin in the intestinal wall are discussed.