Effects of anesthetics on the hepatic metabolism and biliary secretion of lopanoic acid enantiomers in rat

WJ Cooke and LM Cooke

The pharmacokinetics and metabolism of each iopanoate (IOP) enantiomer were studied in male rats anesthetized with urethane, pentobarbital or ether. The only metabolite of IOP that could be detected in bile and plasma was iopanoate glucuronide (IOP-G). Ether and pentobarbital significantly depressed the biliary secretion of each enantiomer as compared with urethane. The anesthetics did not affect differentially the plasma to liver concentration ratio of IOP or the relationship between the hepatic content of IOP-G and the biliary secretion rate of IOP-G for either enantiomer of IOP. At the end of 60 min, the total biliary secretion of (+)-IOP-G was significantly greater than that of (- )-IOP-G in the presence of each anesthetic agent. There was no apparent difference between (+)- and (-)-IOP with respect to hepatic accumulation. There were marked differences between the enantiomers with respect to the hepatic content of IOP-G. At the termination of the experiments, the relationship between the liver content of IOP-G and biliary secretion of IOP-G was not linear. Below a liver IOP-G content of approximately 0.12 mumol/g, the biliary secretion of (-)-IOP-G exceeded that of (+)-IOP-G. Above a liver IOP-G content of 0.12 mumol/g, the biliary secretion of (+)-IOP-G exceeded that of (-)-IOP-G. These data suggest a stereoselectivity with respect to the biliary secretion of IOP enantiomers.

Volume 225, Issue 1, pp. 85-93, 04/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics