Lowenthal D T, Briggs W A, Levy G
J Clin Invest. 1974 Nov;54(5):1221-6. doi: 10.1172/JCI107865.
The objectives of this research were to determine the kinetics of salicylate elimination in anephric patients and particularly to establish if these patients form the major metabolite of salicylic acid, salicyluric acid, at a normal rate. This investigation was initiated because of conflicting reports concerning the contribution of the kidneys to the formation of salicyluric acid in man. Six patients, 20-44 yr old, three of whom were anatomically anephric while the other three were physiologically anephric, received an intravenous injection of 500 mg salicylic acid (as sodium salicylate)/1.73 m(2) body surface area on an interdialysis day. Serial blood samples were obtained for 12 or 16 h after injection and the plasma was assayed for salicylic acid, salicyluric acid, total protein, albumin, and creatinine. Detailed pharmacokinetic analysis based on an open, two-compartment linear model revealed no significant differences in apparent volume of distribution and apparent first-order distribution and elimination rate constants between the anephric patients and normal adult subjects. An estimate of salicyluric acid formation rate by the anephric patients, based on the initial rate of increase of salicylurate concentrations in plasma, indicates that the metabolite is formed at a normal rate. These results suggest that the kidneys do not contribute significantly to the formation of salicyluric acid from salicylic acid in man.
本研究的目的是确定无肾患者中水杨酸盐消除的动力学,尤其是确定这些患者是否以正常速率形成水杨酸的主要代谢产物水杨尿酸。开展这项研究是因为关于肾脏对人体水杨尿酸形成的贡献存在相互矛盾的报道。6名年龄在20至44岁之间的患者,其中3名解剖学上无肾,另外3名生理上无肾,在透析间期接受了每1.73平方米体表面积静脉注射500毫克水杨酸(以水杨酸钠形式)。注射后12或16小时采集系列血样,测定血浆中的水杨酸、水杨尿酸、总蛋白、白蛋白和肌酐。基于开放的二室线性模型进行的详细药代动力学分析显示,无肾患者与正常成年受试者之间在表观分布容积以及表观一级分布和消除速率常数方面无显著差异。根据血浆中水杨尿酸盐浓度的初始增加速率对无肾患者水杨尿酸形成速率的估计表明,该代谢产物以正常速率形成。这些结果表明,在人体中,肾脏对水杨酸形成水杨尿酸的贡献不大。