Mean residence times and distribution volumes for drugs undergoing linear reversible metabolism and tissue distribution and linear or nonlinear elimination from the central compartments

Pharm Res. 1991 Apr;8(4):508-11. doi: 10.1023/a:1015811514050.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Computer Simulation
  • Mathematical Computing
  • Methods
  • Models, Biological*
  • Pharmaceutical Preparations / metabolism*
  • Pharmacokinetics*
  • Tissue Distribution


  • Pharmaceutical Preparations