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Volumes of distribution.

P L Toutain1, A Bousquet-Mélou

  • 1UMR 181 Physiopathologie et Toxicologie Expérimentales INRA/ENVT, Ecole Nationale Vétérinaire de Toulouse, Toulouse cedex 03, France. pl.toutain@envt.fr

Journal of Veterinary Pharmacology and Therapeutics
|December 17, 2004
PubMed
Summary

Understanding drug distribution is key. Different volumes of distribution, like V(ss) and V(area), help calculate loading doses and drug amounts, guiding early drug development for optimal half-life.

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Area of Science:

  • Pharmacokinetics and Drug Metabolism
  • Quantitative Pharmacology
  • Drug Development Science

Background:

  • Volumes of distribution relate total body drug amount to plasma concentration.
  • Plasma drug concentrations can be measured under various conditions, necessitating distinct volume definitions.
  • Key volumes include volume of distribution at equilibrium (V(ss)) and during pseudo-equilibrium (V(area)).

Purpose of the Study:

  • To define and differentiate key volumes of distribution.
  • To explain the utility of V(ss) and V(area) in pharmacokinetic calculations.
  • To highlight the importance of volume of distribution in early drug development and drug selection.

Main Methods:

  • Defining volumes of distribution based on drug concentration-time profiles.
  • Utilizing physiological models to interpret drug distribution, including plasma and tissue binding.
  • Analyzing the relationship between volume of distribution, clearance, and terminal half-life.

Main Results:

  • V(ss) is crucial for calculating loading doses.
  • V(area) is used to determine the residual drug amount in the body from plasma concentrations.
  • Large volumes of distribution can predict a long terminal half-life, even with high clearance.

Conclusions:

  • Accurate determination of volumes of distribution is essential early in drug development.
  • Volume of distribution provides insights into drug distribution and disposition.
  • Selecting drugs with large volumes of distribution can be a strategy for achieving long terminal half-lives.

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