Effects of phenylbutazone, tolbutamide, and clofibric acid on binding of racemic warfarin and its enantiomers to human serum albumin.
The effect of phenylbutazone, tolbutamide, and clofibric acid on the binding of racemic warfarin and its enantiomers to human serum albumin was studied by equilibrium dialysis. Warfarin had one primary and two secondary binding sites on the albumin molecule. No difference in binding was detected at the primary binding site; the extent of R(+)-isomer binding at the secondary binding sites was 2.5 times greater than the corresponding S(-)-isomer binding. Phenylbutazone and warfarin appear to compete for the same primary binding site on the albumin molecule. Tolbutamide interferes with the binding of warfarin enantiomers at their secondary sites. Clofibric acid has a less pronounced effect on warfarin binding than does phenylbutazone or tolbutamide.
D001667:Binding, Competitive; D002994:Clofibrate / Q000031:analogs & derivatives*; D002995:Clofibric Acid / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D010653:Phenylbutazone / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D012709:Serum Albumin / Q000378:metabolism*; D013237:Stereoisomerism; D014044:Tolbutamide / Q000494:pharmacology*; D014859:Warfarin / Q000097:blood*
D012709:Serum Albumin; D002995:Clofibric Acid; D014859:Warfarin; D014044:Tolbutamide; D010653:Phenylbutazone; D002994:Clofibrate