Development and Validation of a Physiology-Based Model for the Prediction of Oral Absorption in Monkeys

Pharm Res. 2007 Jul;24(7):1275-82. doi: 10.1007/s11095-007-9247-y. Epub 2007 Mar 21.

Abstract

Purpose: The development and validation of a physiology-based absorption model for orally administered drugs in monkeys is described.

Materials and methods: Physiological parameters affecting intestinal transit and absorption of an orally administered drug in monkeys have been collected from the literature and implemented in a physiological model for passive absorption previously developed for rats and humans. Predicted fractions of dose absorbed have been compared to experimentally observed values for a set of N = 37 chemically diverse drugs. A sensitivity analysis was performed to assess the influence of various physiological model parameters on the predicted fraction dose absorbed.

Results: A Pearson's correlation coefficient of 0.94 (95% confidence interval: [0.88, 0.97]; p < 0.0001) between the predicted and observed fraction dose absorbed in monkeys was obtained for compounds undergoing non-solubility limited passive absorption (N = 29). The sensitivity analysis revealed that the predictions of fractions dose absorbed in monkeys are very sensitive with respect to inter-individual variations of the small intestinal transit time.

Conclusions: The model is well suited to predict the fraction dose absorbed of passively absorbed compounds after oral administration and to assess the influence of inter-individual physiological variability on oral absorption in monkeys.

Publication types

  • Comparative Study
  • Validation Study

MeSH terms

  • Administration, Oral
  • Animals
  • Gastrointestinal Transit*
  • Humans
  • Intestinal Absorption*
  • Macaca mulatta
  • Models, Biological*
  • Pharmaceutical Preparations / administration & dosage
  • Pharmaceutical Preparations / metabolism*
  • Pharmacokinetics*
  • Rats
  • Reproducibility of Results
  • Species Specificity

Substances

  • Pharmaceutical Preparations