Steady-state volume of distribution of two-compartment models with simultaneous linear and saturated elimination

Abstract The model-independent estimation of physiological steady-state volume of distribution ( \(V_{dss,p}\) ), often referred to non-compartmental analysis (NCA), is historically based on the linear compartment model structure with central elimination. However the NCA-based steady-state volume of distribution ( \(V_{dss,nca}\) ) cannot be generalized to more complex models. In the current paper, two-compartment models with simultaneous first-order and Michaelis–Menten elimination are considered. In particular, two indistinguishable models \(\mathrm{M}_1\) and \(\mathrm{M}_2\) , both having central Michaelis–Menten elimination, while first-order elimination exclusively either from central or peripheral compartment, are studied. The model-based expressions of the steady-state volumes of distribution \(V_{dss,\mathrm{M}_i}\,\,(i=1,2)\) and their relationships to NCA-based \(V_{dss,nca}\) are derived. The impact of non-linearity a...
Source: Journal of Pharmacokinetics and Pharmacodynamics - Category: Drugs & Pharmacology Source Type: research