The effect of various drugs on the binding of warfarin-14C to human albumin.

Abstract The effect of various drugs on the binding of warfarin- 14 C to human albumin was studied by the technique of ultrafiltration. Phenylbutazone, d -thyroxine, sulfa-phenazole, and chlorophenoxyisobutyric acid (CPIB) were less effective than unlabeled warfarin in displacing warfarin- 14 C from albumin. The organic bases, phenyramidol and atropine, had little displacing effect. Phenylbutazone competitively inhibits the binding of warfarin- 14 C to albumin. CPIB binds to a different site on albumin than does warfarin- 14 C and noncompetitively inhibits the binding of the anticoagulant. Both Phenylbutazone and CPIB, at concentrations observed clinically, increased the unbound fraction of warfarin- 14 C 10-fold and 4-fold respectively. Phenyramidol and d -thyroxine had no effect on the binding of warfarin- 14 C under similar circumstances. Decreased binding of coumarin-type drugs to albumin produced by the administration of other drugs may cause an increased anticoagulant effect in clinical situations.

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