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Constant-Rate Intravenous Infusion Methods for Estimating Steady-State Volumes of Distribution and Mean Residence Times in the Body for Drugs Undergoing Reversible Metabolism

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Abstract

Equations for the steady-state volumes of distribution (V ss) and the mean residence times in the body (MRT) are derived for a drug and its metabolite subject to reversible metabolism and separately infused intravenously at a constant rate to steady state of both compounds. The V ss and MRT parameters are functions of the integrals of plasma concentrations, plasma concentrations at steady state, and times to reach steady state of both drug and metabolite. In addition, the MRT values are functions of the infusion rates. These equations were validated by computer simulations and comparison with IV bolus dose parameters. These relationships extend the ability to assess the pharmacokinetics of linear reversible metabolic systems.

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Authors and Affiliations

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

    Haiyung Cheng & William J. Jusko

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

    Haiyung Cheng

Authors
  1. Haiyung Cheng
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  2. William J. Jusko
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Cheng, H., Jusko, W.J. Constant-Rate Intravenous Infusion Methods for Estimating Steady-State Volumes of Distribution and Mean Residence Times in the Body for Drugs Undergoing Reversible Metabolism. Pharm Res 7, 628–632 (1990). https://doi.org/10.1023/A:1015874329265

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  • DOI: https://doi.org/10.1023/A:1015874329265

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