The application of allometric scaling principles to predict pharmacokinetic parameters across species

Expert Opin Drug Metab Toxicol. 2014 Sep;10(9):1241-53. doi: 10.1517/17425255.2014.934671. Epub 2014 Jul 2.

Abstract

Introduction: Interspecies allometric scaling provides a simple and fast option to interpolate or extrapolate drug dose or pharmacokinetic parameters to a species of interest. Over the years, new scaling methods have been developed in order to improve the performance of these predictions. It is critical to choose appropriate allometric scaling approach(es) to analyze the available pharmacokinetic data.

Areas covered: This review provides updated information on the latest allometric scaling methods developed for the most frequently interpolated or extrapolated pharmacokinetic parameters. The different degrees of success and advantages/disadvantages of different methods are compared and contrasted. The pitfalls that affect the accuracy of prediction and the solutions to avoid the risk of prediction errors are discussed. The application of allometric scaling in veterinary medicine is presented.

Expert opinion: Although interspecies allometric scaling needs further refinements and has limitations, it is still a potential tool and rational option for the estimate of pharmacokinetic parameters in species for which there are no data available or to better interpret preclinical efficacy and safety trials. Allometric scaling can offer insight into possible mechanisms of species-dependent drug disposition.

Keywords: allometric scaling; clearance; comparative pharmacology; elimination half-life; interspecies pharmacokinetics; veterinary medicine; volume of distribution.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Humans
  • Models, Theoretical*
  • Pharmaceutical Preparations / administration & dosage
  • Pharmaceutical Preparations / metabolism*
  • Pharmacokinetics*
  • Species Specificity
  • Veterinary Drugs / administration & dosage
  • Veterinary Drugs / pharmacokinetics

Substances

  • Pharmaceutical Preparations
  • Veterinary Drugs