Accumulationof IndoxylSulfate, an Inhibitorof Drug-Binding,in UremicSerum as Demonstrated by Internal-SurfaceReversed-Phase LiquidChromatography

We quantified indoxyl sulfate in uremic serum by using internal-surface reversed-phase high-performance liquid chromatography. Its concentrations were markedly in-creased in chronic hemodialysis patients, and were signifi-cantly but weakly correlated with the concentrations of creati-nine and f32-microglobulinin these patients ’ serum, and with the duration of their hemodialysis treatment. Indoxyl sulfate could not be removed effectively by conventional hemodialy-sis because of its strong binding to serum albumin. Equilibri-um dialysis demonstrated that indoxyl sulfate inhibited the binding of salicylate to albumin, and that 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid inhibited the binding of indoxyl sulfate to albumin. Inconclusion, indoxyl sulfate was marked-ly accumulated in uremic serum, and inhibited drug binding. AdditIonal Keyphrases: hemodialysis albumin binding of drugs- salicylafe Albumin binding of many acidic drugs is well known to be decreased in serum from uremic patients (1-3). At present the reduction of drug-binding is considered to be due to the accumulation of several endogenous albumin-bound metab-olites that competitively inhibit the albumin binding of drugs. So far, several endogenous metabolites have been proposed as inhibitors of drug-binding, including hippuri