Wagner J G, Szpunar G J, Ferry J J
J Pharmacokinet Biopharm. 1985 Feb;13(1):73-92. doi: 10.1007/BF01073657.
The two-compartment model of Rowland et al., (2) has been extended by replacing first order elimination with Michaelis-Menten elimination kinetics. All of the equations for steady-state concentrations and clearances for zero order (constant rate) input orally (into compartment #2) and intravenously (into compartment #1) are derived and reported. The steady-state concentration in compartment #1, following intravenous administration, is shown to be a nonlinear function of maximal velocity of metabolism, Vm, the Michaelis constant, Km, and liver blood flow, Q; and, following oral administration is dependent only upon Vm and Km and is independent of Q. However, oral bioavailability is a function of Vm, Km, and Q. The model allows physiologic pharmacokinetic interpretation of both linear and nonlinear data; and, together with simple modification of the model, can explain much observed pharmacokinetic data to date particularly for first-pass drugs. Future articles in the series will be concerned with single doses, evaluation of literature data in terms of the model, application of the theory in toxicology and in clinical pharmacokinetics and therapeutics.
罗兰等人（2）的二室模型已得到扩展，用米氏消除动力学取代了一级消除。推导并报告了口服（进入第2室）和静脉注射（进入第1室）零级（恒速）输入的稳态浓度和清除率的所有方程。静脉给药后，第1室的稳态浓度显示为代谢最大速度Vm、米氏常数Km和肝血流量Q的非线性函数；口服给药后，仅取决于Vm和Km，与Q无关。然而，口服生物利用度是Vm、Km和Q的函数。该模型允许对线性和非线性数据进行生理药代动力学解释；并且，通过对模型的简单修改，至今可以解释许多观察到的药代动力学数据，特别是对于首过效应药物。该系列的后续文章将涉及单剂量、根据模型对文献数据的评估、该理论在毒理学以及临床药代动力学和治疗学中的应用。
