Ashton J M, Bolme P, Zerihun G
Dept. of Biopharmaceutics and Pharmacokinetics, Biomedical Centre, Uppsala University, Sweden.
J Pharm Pharmacol. 1989 Jul;41(7):474-80. doi: 10.1111/j.2042-7158.1989.tb06503.x.
The serum protein binding of salicylic and salicyluric acid has been determined by ultrafiltration in 60 children after administration of oral salicylate. The children were classified according to nutritional status: well-nourished (n = 12), underweight (n = 12), marasmic (n = 17) marasmic-kwashiorkor (n = 7) and kwashiorkor (n = 12). Salicylic acid free fractions were 0.106 +/- 0.026, 0.114 +/- 0.069, 0.141 +/- 0.037, 0.285 +/- 0.279 and 0.438 +/- 0.190 in the five groups, respectively. Salicyluric acid free fractions were 0.184 +/- 0.057, 0.280 +/- 0.282, 0.236 +/- 0.114, 0.484 +/- 0.497 and 0.646 +/- 0.261, respectively. The degree of binding was dependent on serum albumin levels, ligand concentrations and non-esterified fatty acids (NEFA). The NEFA/albumin ratio ranged from 0.05 to 6.6. The fitting of a one-site Scatchard binding model to the collective data was improved when a decrease was allowed for in the number of binding sites in proportion to NEFA concentrations. Salicyluric acid binding could be fitted only when inhibition of the parent compound was included. Binding was not affected by age or sex. The major determinants of salicylate binding in sera from malnourished children have thus been identified.
在60名儿童口服水杨酸盐后，通过超滤法测定了水杨酸和水杨尿酸的血清蛋白结合率。这些儿童根据营养状况进行分类：营养良好（n = 12）、体重不足（n = 12）、消瘦（n = 17）、消瘦 - 夸希奥科病（n = 7）和夸希奥科病（n = 12）。五组中水杨酸的游离分数分别为0.106±0.026、0.114±0.069、0.141±0.037、0.285±0.279和0.438±0.190。水杨尿酸的游离分数分别为0.184±0.057、0.280±0.282、0.236±0.114、0.484±0.497和0.646±0.261。结合程度取决于血清白蛋白水平、配体浓度和非酯化脂肪酸（NEFA）。NEFA/白蛋白比值范围为0.05至6.6。当允许结合位点数量与NEFA浓度成比例减少时，将单点Scatchard结合模型应用于汇总数据的拟合效果得到改善。只有当包括母体化合物的抑制作用时，水杨尿酸结合才能拟合。结合不受年龄或性别的影响。因此，已确定了营养不良儿童血清中水杨酸盐结合的主要决定因素。
