Lane E A, Levy R H
J Pharm Sci. 1983 Nov;72(11):1352-4. doi: 10.1002/jps.2600721130.
The dose-dependent nonlinearity of the clearance of cinromide, a medium extraction ratio drug, has been established in two monkeys. Special problems encountered in evaluation of nonlinearity of such drugs were resolved by the experimental design: cinromide was infused to steady state via the portal vein. A linearized form of the Michaelis-Menten equation was used to determine Vmax and Km. In addition, cinromide was administered to one of the monkeys via a femoral vein to verify the overestimation of Km by administration at a peripheral venous site.
环丙贝特是一种中等肝提取率药物，在两只猴子身上已证实其清除存在剂量依赖性非线性。通过实验设计解决了评估此类药物非线性时遇到的特殊问题：环丙贝特经门静脉输注至稳态。采用米氏方程的线性化形式来确定Vmax和Km。此外，通过股静脉给其中一只猴子给药环丙贝特，以验证经外周静脉给药时对Km的高估情况。
