Abstract
The decreased binding of anionic drugs to serum protein in chronic renal failure (CRF) is now well documented. We previously reported that 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) is a major endogenous protein binding substance and a drug-binding inhibitor retained in CRF serum. CMPF inhibits phenytoin and dyes binding to serum protein and serum albumin at the concentrations usually observed in CRF serum. Taking into consideration the hypoalbuminemia usually observed in CRF however, CMPF does not entirely account for the impaired phenytoin binding found in CRF serum. This observation suggests the presence of other drug-binding inhibitors, not yet identified, in CRF serum. In this study, we separated serum albumin from normal and CRF sera by fast protein liquid chromatography (FPLC) and ligand affinity chromatography (LAC) using phosphate buffer, pH 7.4, as an eluent, and analyzed the albumin-binding ligands by reversed-phase high performance liquid chromatography (HPLC). The HPLC peak having the highest UV absorbance was only CMPF in both samples obtained from FPLC and LAC. Weak albumin-binding substances such an indoxyl sulfate were not detected. These results indicate that the only major potent albumin-binding substance may be CMPF and that retention of other potent binding substances is scarce in CRF serum. These observations suggest that the weak binding substances retained in CRF serum contribute to a certain extent to the inhibition of protein binding observed for some drugs in CRF.
