Influence of chronic renal failure and hemodialysis on diflunisal plasma protein binding
Influence of chronic renal failure and hemodialysis on diflunisal plasma protein binding
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慢性肾功能衰竭和血液透析对二氟尼血浆蛋白结合的影响
DOI：
10.1038/clpt.1980.89
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发表时间：
1980
影响因子：
6.7
通讯作者：
P. De Schepper
中科院分区：
文献类型：
--
作者：
R. Verbeeck;P. De Schepper
用平衡透析法研究了健康、尿毒症和老年受试者血浆中37°平衡透析法的二氟尼柳蛋白结合情况。假设两类独立的结合位点(Scatchard模型)，对结合数据进行计算机分析。尿毒症患者血浆二氟尼柳-白蛋白相互作用的主要结合常数K1(2.39±0.29×105M−1)显著低于正常血浆(6.86±0.59×105M−1)。尿毒症患者和正常人血浆中初级二氟尼柳结合位点(N1)的数目无明显差异。老年血浆K_1和N_1均与正常值无差异，提示老年人血浆蛋白结合力降低是由于血浆白蛋白浓度降低所致。尿毒症患者血液透析过程中与血浆的结合研究表明，游离二氟尼柳由透析开始时的0.46±0.04%上升到透析结束时的0.61±0.06%。血浆游离脂肪酸浓度也有类似的上升。体外置换研究表明，油酸是二氟尼柳与人血清白蛋白结合的竞争性抑制剂。这可能解释了血液透析治疗结束时二氟尼柳血浆结合力下降的原因。
Diflunisal protein binding was studied by equilibrium dialysis at 37° in plasma from healthy, uremic, and geriatric subjects. Binding data were computer analyzed assuming 2 classes of independent binding sites (Scatchard model). K1, the primary association constant for the diflunisal‐albumin interaction, was substantially lower in uremic plasma (2.39 ± 0.29 × 105M−1) than in normal plasma (6.86 ± 0.59 × 105 M−1). No difference was found between the number of primary diflunisal binding sites (N1) in uremic and normal plasma. In geriatric plasma neither K1 nor N1 differed from the normal values, indicating that decreased diflunisal plasma protein binding in the elderly is a result of lower plasma albumin concentration. Binding studies with plasma from uremic patients during hemodialysis revealed that free diflunisal rose from 0.46 ± 0.04% at the start to 0.61 ± 0.06% at the end of dialysis. Plasma free fatty acid concentrations rose similarly. In vitro displacement studies showed that oleic acid is a competitive inhibitor for the binding of diflunisal to human serum albumin. This may explain the decrease in diflunisal plasma binding at the end of hemodialysis treatment.