Animal versus human oral drug bioavailability: do they correlate?

Eur J Pharm Sci. 2014 Jun 16;57(100):280-91. doi: 10.1016/j.ejps.2013.08.018. Epub 2013 Aug 26.

Abstract

Oral bioavailability is a key consideration in development of drug products, and the use of preclinical species in predicting bioavailability in human has long been debated. In order to clarify whether any correlation between human and animal bioavailability exist, an extensive analysis of the published literature data was conducted. Due to the complex nature of bioavailability calculations inclusion criteria were applied to ensure integrity of the data. A database of 184 compounds was assembled. Linear regression for the reported compounds indicated no strong or predictive correlations to human data for all species, individually and combined. The lack of correlation in this extended dataset highlights that animal bioavailability is not quantitatively predictive of bioavailability in human. Although qualitative (high/low bioavailability) indications might be possible, models taking into account species-specific factors that may affect bioavailability are recommended for developing quantitative prediction.

Keywords: Drug development; First in man pharmacokinetics; Oral drug absorption.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Biopharmaceutics / methods*
  • Humans
  • Linear Models
  • Models, Animal
  • Models, Biological
  • Pharmaceutical Preparations / administration & dosage*
  • Pharmaceutical Preparations / chemistry
  • Pharmaceutical Preparations / metabolism*
  • Pharmacokinetics*
  • Species Specificity

Substances

  • Pharmaceutical Preparations