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
More News: Drugs & Pharmacology | Men