COMPARISON OF DRUG-BINDING INTERACTIONS ON HUMAN, RAT AND RABBIT SERUM-ALBUMIN USING HIGH-PERFORMANCE DISPLACEMENT CHROMATOGRAPHY

The binding of warfarin, a series of non-steroidal anti-inflammatory d rugs and a series of benzodiazepines to rat serum albumin (RatSA) and rabbit serum albumin (RabSA) was compared with their binding to human serum albumin (HSA) using high-performance liquid chromatography on st ationary phases based on immobilized albumins. The effect of the addit ion to the mobile phase of compounds known to bind to HSA at site I (p henylbutazone) or at site II (R- and S-ibuprofen) or at both sites (2, 3,5-triiodobenzoic acid) was investigated on all three proteins. The r esults indicated that for the chiral compounds studied, the stereosele ctivity of drug binding was much lower on RatSA than on HSA. On RatSA and RabSA, the benzodiazepine site was not a major binding site for R- and S-ibuprofen, The results indicated the existence of two binding s ites for R and S warfarin on RatSA and probably on RabSA. On RatSA, on e site is the major stereoselective site and is the major binding site of phenylbutazone and piroxicam, The other one is a major binding sit e for R- and S-ibuprofen and R- and S-ketoprofen.