Craig W A, Evenson M A, Sarver K P, Wagnild J P
J Lab Clin Med. 1976 Apr;87(4):637-47.
Protein binding of numerous drugs, primarily organic acids, is decreased in sera from uremic patients. The defect in binding is (1) greater than can be accounted for by hypoalbuminemia alone; (2) unchanged by prolonged in vitro dialysis; (3) transferred in the protein but not the ultrafiltrate fraction of uremic serum; and (4) not reproduced by addition of low and middle molecular weight compounds known to accumulate in uremia. However, treatment with activated charcoal at pH3 was found to significantly increase drug protein binding in uremic sera. This effect was studied with six different drugs in sera from groups of 6 normal subjects and 8 patients on chronic hemodialysis. The percentage of sulfamethoxazole, dicloxacillin, diphenylhydantoin, salicylate, and digitoxin bound to protein in normal sera (65.9, 97.1, 93.1, 96.7, and 92.7, respectively) was unchanged by charcoal treatment. In contrast, charcoal treatment significantly (p less than 0.01) increased the percentage of drug bound to protein in uremic sera from 41.7 to 59.0 for sulfamethoxazole, 90.7 to 96.3 for dicloxacillin, 84.3 to 90.8 for diphenyhydantoin, 86.4 to 93.8 for salicylate, and 89.5 to 90.9 for digitoxin. Charcoal treatment significantly (p less than 0.05) reduced penicillin protein binding in normal sera and failed to correct the binding defect for penicillin in uremic sera. The effect of charcoal can be explained by removal of an inhibitor which accumulates in uremia and (1) occupies the binding site of certain drugs, (2) changes the configuration of the albumin molecule, or (3) both. Free fatty acid (FFA) concentrations in uremic patients were similar to those in normal subjects and were not the cause of the binding defect.
许多药物（主要是有机酸）与蛋白质的结合在尿毒症患者的血清中有所减少。结合缺陷表现为：（1）程度大于仅由低白蛋白血症所能解释的；（2）长时间体外透析后无变化；（3）存在于尿毒症血清的蛋白质部分而非超滤部分；（4）添加已知在尿毒症中蓄积的低分子量和中分子量化合物无法重现该缺陷。然而，发现用pH3的活性炭处理可显著增加尿毒症血清中的药物蛋白质结合。用6种不同药物在6名正常受试者和8名慢性血液透析患者的血清中研究了这种效应。正常血清中与蛋白质结合的磺胺甲恶唑、双氯西林、苯妥英、水杨酸盐和地高辛的百分比（分别为65.9%、97.1%、93.1%、96.7%和92.7%）经活性炭处理后无变化。相比之下，活性炭处理显著（p小于0.01）增加了尿毒症血清中与蛋白质结合的药物百分比，磺胺甲恶唑从41.7%增至59.0%，双氯西林从90.7%增至96.3%，苯妥英从84.3%增至90.8%，水杨酸盐从86.4%增至93.8%，地高辛从89.5%增至90.9%。活性炭处理显著（p小于0.05）降低了正常血清中青霉素与蛋白质的结合，且未能纠正尿毒症血清中青霉素的结合缺陷。活性炭的作用可通过去除一种在尿毒症中蓄积的抑制剂来解释，该抑制剂（1）占据某些药物的结合位点，（2）改变白蛋白分子的构型，或（3）两者兼有。尿毒症患者的游离脂肪酸（FFA）浓度与正常受试者相似，并非结合缺陷的原因。
