TY - JOUR T1 - Species-dependent enantioselective plasma protein binding of MK-571, a potent leukotriene D4 antagonist. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 484 LP - 487 VL - 18 IS - 4 AU - J H Lin AU - F A deLuna AU - E H Ulm AU - D J Tocco Y1 - 1990/07/01 UR - http://dmd.aspetjournals.org/content/18/4/484.abstract N2 - The plasma protein binding of the enantiomers of MK-571 was stereoselective and the stereoselectivity was species dependent. The 12 mammalian species studied could be classified into three groups: those that bind the S-(+)-enantiomer to a greater extent than the R-(-)-enantiomer (human, baboon, monkey, cow, dog, and cat); those that bind the R-(-)-enantiomer more extensively (rat, guinea pig, and sheep); and those that show no stereoselectivity (rabbit, hamster, and mouse). The stereoselective binding appears to have no phylogenetic relationship. Using serum albumin instead of plasma, a similar degree of stereoselective binding was observed for human, dog, sheep, and rat, suggesting that albumin is the major binding component for MK-571 enantiomers, and that species differences in stereoselective binding are likely due to structural differences in the albumin molecule. Displacement studies with [14C] diazepam, [14C]warfarin, and [3H]digitoxin indicated that the enantioselective differences in protein binding are most likely due to the differences in binding affinity rather than to different binding sites. ER -