title: Mean residence times and distribution volumes for drugs undergoing linear reversible metabolism and tissue distribution and linear or nonlinear elimination from the central compartments.
abstract: Equations for the mean residence times in the body (MRT) and in the central compartment (MRTc) are derived for bolus central dosing of a drug and its metabolite which undergo linear tissue distribution and linear reversible metabolism but are eliminated either linearly or nonlinearly (Michaelis-Menten kinetics) from the central compartments. In addition, a new approach to calculate the steady-state volumes of distribution for nonlinear systems (reversible or nonreversible) is proposed based on disposition decomposition analysis. The application of these equations to a dual reversible two-compartment model is illustrated by computer simulations.
authors.affiliation: Department of Pharmacokinetics and Drug Metabolism, Merrell Dow Research Institute, Indianapolis, Indiana 46268.
authors.forename: H Y
authors.initials: HY
authors.lastname: Cheng
authors.forename: W J
authors.initials: WJ
authors.lastname: Jusko
mesh_terms: D003198:Computer Simulation; D008432:Mathematical Computing; D008722:Methods; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D014018:Tissue Distribution
chemical_list: D004364:Pharmaceutical Preparations