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Abstract
In chronic renal failure, substances that are effectively excreted in healthy subjects
accumulate in serum. These substances, uremic toxins, include a variety of organic
acids. It has been reported that a decrease in the bilirubin (BR) binding capacity
occurs in the serum of renal failure patients. 3-Carboxy-4-methyl-5-propyl-2-furanpropanoic
acid (CMPF) has a high affinity for human serum albumin (HSA) and is a potent inhibitor
of the serum protein binding of many drugs. We recently reported that CMPF and BR
share the binding site for dicarboxylate molecules on the HSA molecule [Pharm Res
1999;16:916–923]. In this study, in order to confirm whether CMPF is involved in the
decrease of BR serum binding capacity in chronic renal failure patients, the total
concentrations of uremic toxins, CMPF, and indoxyl sulfate (IS) and the free BR concentration
in serum from healthy volunteers and renal failure patients were determined. Both
total CMPF and IS concentrations correlate with the free BR concentration. However,
results from the peroxidase method reveal that IS cannot displace BR under the physiological
condition [IS]/[HSA] <1. We, therefore, conclude that CMPF is one of the substances
which contribute to the decreased binding capacity of BR in uremic serum.