Tsutsumi Y, Maruyama T, Takadate A, Shimada H, Otagiri M
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Nephron. 2000 May;85(1):60-4. doi: 10.1159/000045631.
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.
在慢性肾衰竭中，健康受试者中能有效排泄的物质会在血清中蓄积。这些物质，即尿毒症毒素，包括多种有机酸。据报道，肾衰竭患者血清中胆红素（BR）结合能力会下降。3 - 羧基 - 4 - 甲基 - 5 - 丙基 - 2 - 呋喃丙酸（CMPF）对人血清白蛋白（HSA）具有高亲和力，并且是许多药物血清蛋白结合的强效抑制剂。我们最近报道，CMPF和BR在HSA分子上共享二羧酸盐分子的结合位点[《药物研究》1999年；16:916 - 923]。在本研究中，为了确认CMPF是否与慢性肾衰竭患者血清BR结合能力下降有关，测定了健康志愿者和肾衰竭患者血清中尿毒症毒素、CMPF和硫酸吲哚酚（IS）的总浓度以及游离BR浓度。CMPF和IS的总浓度均与游离BR浓度相关。然而，过氧化物酶法的结果显示，在生理条件[IS]/[HSA]<1下，IS不能置换BR。因此，我们得出结论，CMPF是导致尿毒症血清中BR结合能力下降的物质之一。
