Wosilait W D
Eur J Clin Pharmacol. 1976 Feb 6;9(4):285-90. doi: 10.1007/BF00561662.
The binding of salicylates by human serum albumin was analyzed by use of a computer program using previously published association constants and binding capacities for the two sets of binding sites on the protein. The analysis consisted of computing free and bound salicylates for a range of therapeutic and toxic concentration from 181 to 7246 mumole/L (25 to 1000 mg/L). At low and therapeutic levels the total amount of bound drug would exceed the amount of free drug. At higher levels, which included therapeutic and toxic ranges, the amount of free drug plasma, up to 2000 mumole/L the high affinity sites (Site 1), would bind most of the drug, but as the concentration of drug increased this site would approach saturation and the low affinity Site 2 would bind increasing amounts of salicylate. At high salicylate levels the amount of drug bound by the low affinity sites. Computation also showed that when the total amount of protein in the analysis was reduced, from 5, 4, 3, to 2 gm%, as in hypoalbuminemia, the total amount of drug bound by the protein would decrease and the quantity of free drug would increase. The amount of drug bound by each of the two sets of sites also fell as the concentration of protein decreased. Some of the possible clinical implications of these findings are discussed.
利用一个计算机程序，借助先前发表的关于蛋白质上两组结合位点的缔合常数和结合能力，分析了人血清白蛋白与水杨酸盐的结合情况。该分析包括计算浓度范围为181至7246微摩尔/升（25至1000毫克/升）的一系列治疗浓度和中毒浓度下的游离和结合水杨酸盐。在低浓度和治疗浓度水平时，结合药物的总量将超过游离药物的量。在较高浓度水平，包括治疗浓度范围和中毒浓度范围，血浆中游离药物量在高达2000微摩尔/升时，高亲和力位点（位点1）会结合大部分药物，但随着药物浓度增加，该位点会接近饱和，低亲和力位点2会结合越来越多的水杨酸盐。在高水杨酸盐水平时，低亲和力位点结合的药物量。计算还表明，当分析中的蛋白质总量从5克%、4克%、3克%降至2克%时，如在低白蛋白血症中，蛋白质结合的药物总量会减少，游离药物量会增加。随着蛋白质浓度降低，两组位点各自结合的药物量也会下降。讨论了这些发现的一些可能的临床意义。
