Bochner F, Graham G G, Cham B E, Imhoff D M, Haavisto T M
Clin Pharmacol Ther. 1981 Aug;30(2):266-75. doi: 10.1038/clpt.1981.158.
Single oral doses of aspirin (ASA, 1,500 mg), sodium salicylate (NaSA, 1,500 mg, 1,200 mg), and salicyluric acid (SUA, 500 mg) were given to five subjects. Serial plasma and urine samples were collected for 24 hr (plasma) and up to 48 hr (urine); salicylic acid (SA), SUA, and gentisic acid (GA) were measured by high-pressure liquid chromatography. The plasma concentration/time profiles for SUA after ASA and NaSA were fitted to the empirical equation CpSUA = A-Bt-Ce-alpha t -- (A-C)e-beta t. Michaelis constants (Vm and Km) for the conversion of SA to SUA were calculated from the equation (formula see text), where Cl is the renal clearance of SUA, ke is the rate constant of elimination of SUA, CpSA is the plasma concentration of salicylic acid. The term Cl (formula see text) is the estimated rate of formation of SUA from SA at any time (t). The calculated values (mean +/- SD) of Vm, Km, and Kmf (Km in terms of unbound SA) were 43.4 +/- 10.1 mg SA/hr, 14.3 +/- 3.4 mg SA/l plasma, and 0.75 +/- 0.15 mg unbound SA/l plasma. The Vm values were in accord with those reported, but the value for Km was considerably lower. Renal clearances of SUA and GA were 340 +/- 51 and 65 +/- 10 ml/min.
对五名受试者分别单次口服阿司匹林（ASA，1500毫克）、水杨酸钠（NaSA，1500毫克、1200毫克）和水杨酸尿酸（SUA，500毫克）。连续采集24小时的血浆样本（血浆）和长达48小时的尿液样本；通过高压液相色谱法测定水杨酸（SA）、SUA和龙胆酸（GA）。将ASA和NaSA给药后SUA的血浆浓度/时间曲线拟合到经验方程CpSUA = A - Bt - Ce-αt - (A - C)e-βt。根据方程（公式见原文）计算SA转化为SUA的米氏常数（Vm和Km），其中Cl是SUA的肾清除率，ke是SUA的消除速率常数，CpSA是水杨酸的血浆浓度。术语Cl（公式见原文）是在任何时间（t）SA形成SUA的估计速率。Vm、Km和Kmf（以未结合SA计的Km）的计算值（平均值±标准差）分别为43.4±10.1毫克SA/小时、14.3±3.4毫克SA/升血浆和0.75±0.15毫克未结合SA/升血浆。Vm值与报道的值一致，但Km值明显较低。SUA和GA的肾清除率分别为340±51和65±10毫升/分钟。
