Mabuchi H, Nakahashi H
Department of Internal Medicine and Nephrology, Nishijin Hospital, Kyoto, Japan.
Ther Drug Monit. 1988;10(3):261-4. doi: 10.1097/00007691-198803000-00003.
Impaired binding of anionic drugs to serum albumin in patients with uremia is thought to be due to the accumulation of endogenous substances that bind to albumin. In this study the displacement by the anionic drugs diazepam, warfarin, and salicylic acid, which are known to be representative drugs for the binding sites on the albumin molecule, of several endogenous ligands that bind to albumin in uremic serum was examined. The free fractions of the ligands bound to albumin were separated by ultrafiltration in the presence and the absence of test drugs and assayed by high-performance liquid chromatography. Diazepam displaced indoxyl sulfate (IS), hippuric acid (HA), and indole-3-acetic acid (IAA), and warfarin displaced IS, HA, ISAA, and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid from serum albumin. However, salicylic acid did not displace the substance examined. The methods reported here are useful for determining the binding sites of the endogenous ligands on albumin and to clarify the drug-ligand interaction on albumin molecule in uremic serum.
尿毒症患者体内阴离子药物与血清白蛋白的结合受损，被认为是由于与白蛋白结合的内源性物质蓄积所致。在本研究中，检测了阴离子药物地西泮、华法林和水杨酸（已知是白蛋白分子上结合位点的代表性药物）对几种与尿毒症血清中白蛋白结合的内源性配体的置换作用。在有和没有测试药物存在的情况下，通过超滤分离与白蛋白结合的配体的游离部分，并采用高效液相色谱法进行测定。地西泮置换了硫酸吲哚酚（IS）、马尿酸（HA）和吲哚 - 3 - 乙酸（IAA），华法林从血清白蛋白中置换了IS、HA、异戊酸（ISAA）和3 - 羧基 - 4 - 甲基 - 5 - 丙基 - 2 - 呋喃丙酸。然而，水杨酸并未置换所检测的物质。本文报道的方法对于确定内源性配体在白蛋白上的结合位点以及阐明尿毒症血清中白蛋白分子上的药物 - 配体相互作用是有用的。
