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Related Experiment Videos

Comparison between permeability coefficients in rat and human jejunum

U Fagerholm1, M Johansson, H Lennernäs

  • 1Department of Pharmacy, University of Uppsala, Sweden.

Pharmaceutical Research
|September 1, 1996
PubMed
Summary

Rat and human jejunum models show high correlation for predicting passive drug absorption. Carrier-mediated transport requires further investigation for accurate animal-to-human scaling. Intestinal viability monitoring is crucial.

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Area of Science:

  • Pharmacokinetics
  • Drug Absorption
  • In Situ Intestinal Permeability

Background:

  • Accurate prediction of oral drug absorption is crucial for drug development.
  • In situ intestinal models offer a controlled environment to study drug permeability.
  • Comparing animal models to human data is essential for translational research.

Purpose of the Study:

  • To determine effective intestinal permeability (Peff) in rat jejunum in situ for diverse compounds.
  • To compare rat in situ Peff values with historical human in vivo Peff data.
  • To evaluate the utility of the rat jejunum model for predicting human oral drug absorption.

Main Methods:

  • Utilized an in situ perfusion model in anesthetized rats.
  • Employed a low perfusion flow rate (0.2 ml/min) in the rat model.

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  • Assessed intestinal viability through physiological function monitoring during perfusion.

    • Main Results:

    • Passive absorption showed a strong correlation between human and rat jejunum Peff (Peff, man = 3.6 x Peff.rat + 0.03.10(-4)).
    • Carrier-mediated absorbed solutes deviated from this correlation, indicating challenges in scaling active transport.
    • Developed an equation to estimate human fraction absorbed (fa) from human Peff values.

    Conclusions:

    • Rat and human jejunum Peff estimates for passive solutes are highly correlated and predict human oral absorption.
    • Scaling of carrier-mediated transport requires further investigation due to potential differences in transport maximum and substrate specificity.
    • Continuous monitoring of intestinal viability using marker compounds is essential for reliable in situ studies.