Cheng H Y, Jusko W J
Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo 14260.
Biopharm Drug Dispos. 1989 Sep-Oct;10(5):513-28. doi: 10.1002/bdd.2510100509.
Equations were examined to predict or correlate steady-state (SS) plasma concentrations and single-dose (SD) data for pharmacokinetic systems with various types of input and nonlinear elimination. The effects of variation of the Michaelis-Menten parameters, input rate of drug, or bioavailability on the predictability of steady-state plasma concentrations from single-dose data were demonstrated by computer simulations for a one-compartment model. Use of apparently linear equations with Michaelis-Menten parameters to predict steady-state plasma concentrations from single dose data is adequate only in limiting low single-dose cases. Linear SS versus SD correlations for both intravenous and oral dosing can be observed in population data only when Km is the principal variable; other conditions produce curvilinear behavior. Equations to calculate values of the Michaelis-Menten parameters from dual single-dose and steady-state AUC values are derived and tested for drugs which are intravenously administered. These equations and simulations provide insight into factors determining the relationship between SS and SD AUC for drugs with nonlinear elimination.
对各种输入类型和非线性消除的药代动力学系统的稳态（SS）血浆浓度和单剂量（SD）数据的预测或相关性方程进行了研究。通过对一室模型的计算机模拟，证明了米氏参数、药物输入速率或生物利用度的变化对单剂量数据预测稳态血浆浓度的影响。仅在低单剂量的极限情况下，使用具有米氏参数的表观线性方程从单剂量数据预测稳态血浆浓度才是合适的。仅当Km是主要变量时，在群体数据中才能观察到静脉注射和口服给药的线性稳态与单剂量相关性；其他情况会产生曲线行为。推导并测试了从双单剂量和稳态AUC值计算米氏参数值的方程，用于静脉给药的药物。这些方程和模拟有助于深入了解决定非线性消除药物的稳态和单剂量AUC之间关系的因素。
