Pharmacokinetics of etodolac enantiomers in the rat after administration of phenobarbital or cimetidine.

The influences of phenobarbital and cimetidine on the pharmacokinetics of etodolac enantiomers were studied in male Sprague-Dawley rats. Phenobarbital caused significant reductions in the AUC of both the active S-enantiomer (24%) and the inactive R-enantiomer of etodolac (26%), and an increase in the urinary excretion of glucuronidated S-etodolac. In bile duct-cannulated rats the initial biliary recoveries of the acyl-glucuronidated etodolac enantiomers were not affected by phenobarbital. In vitro, phenobarbital caused no changes in the hepatic microsomal net glucuronidation of etodolac enantiomers after phenobarbital, although it did result in significant increases in the apparent oxidative metabolism of both enantiomers. Therefore, phenobarbital seems to cause an enhanced CL of etodolac by induction of hepatic non-conjugative metabolism. Cimetidine had no discernible effect on the pharmacokinetics of etodolac enantiomers.