STEREOSELECTIVE PHARMACOKINETICS OF OXPRENOLOL, PROPRANOLOL, AND VERAPAMIL - SPECIES-DIFFERENCES AND INFLUENCE OF ENDOTOXIN

The influence of endotoxin-induced inflammation was studied on the pha rmacokinetics of the enantiomers of the racemic drugs oxprenolol, prop ranolol and verapamil in rabbits and dogs. Enantioselective pharmacoki netics were seen for oxprenolol and propranolol in the rabbit and for propranolol and verapamil in the dog. In the dog, the enantioselective differences in plasma concentrations are due to differences in both p rotein binding and metabolism, whereas in the rabbit the differences a re due solely to differences in metabolism. In both species endotoxin treatment increases the plasma concentrations of the enantiomers of th e three drugs; both protein binding and metabolism are influenced. In rabbits and in dogs, the influence of endotoxin on the disposition of the three drugs is less enantioselective than was previously observed in the rat. (C) 1995 Wiley-Liss, Inc.