Mean residence times and distribution volumes for drugs undergoing linear reversible metabolism and tissue distribution and linear or nonlinear elimination from the central compartments.
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.
Cheng
H Y
HY
Department of Pharmacokinetics and Drug Metabolism, Merrell Dow Research Institute, Indianapolis, Indiana 46268.
Jusko
W J
WJ
D003198:Computer Simulation; D008432:Mathematical Computing; D008722:Methods; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D014018:Tissue Distribution
D004364:Pharmaceutical Preparations