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Mean Residence Times and Distribution Volumes for Drugs Undergoing Linear Reversible Metabolism and Tissue Distribution and Linear or Nonlinear Elimination from the Central Compartments

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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.

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Author notes

  1. Haiyung Cheng

    Present address: Department of Drug Metabolism, Merck Sharp &, Dohme Research Laboratories, West Point, Pennsylvania, 19486

Authors and Affiliations

  1. Department of Pharmacokinetics and Drug Metabolism, Merrell Dow Research Institute, Indianapolis, Indiana, 46268

    Haiyung Cheng

  2. Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, Buffalo, New York, 14260

    Haiyung Cheng & William J. Jusko

Authors
  1. Haiyung Cheng
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  2. William J. Jusko
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Cheng, H., Jusko, W.J. 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 8, 508–511 (1991). https://doi.org/10.1023/A:1015811514050

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  • DOI: https://doi.org/10.1023/A:1015811514050

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