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Related Experiment Videos

Regional difference in P-glycoprotein function in rat intestine.

Aiko Iida1, Mikio Tomita, Masahiro Hayashi

  • 1Department of Drug Absorption and Pharmacokinetics, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. iida_aiko@allergan.com

Drug Metabolism and Pharmacokinetics
|April 28, 2005
PubMed
Summary

Inhibition of P-glycoprotein (P-gp) enhances the absorption of P-gp substrates like rhodamine123 in the jejunum and ileum, but not the colon. This study confirms in vitro findings at a whole-body level, highlighting regional differences in P-gp activity.

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Area of Science:

  • Pharmacokinetics
  • Drug Absorption
  • Gastrointestinal Physiology

Background:

  • P-glycoprotein (P-gp) efflux transporters significantly impact drug absorption.
  • In vitro studies suggest P-gp inhibition improves P-gp substrate absorption.
  • Translating in vitro findings to in vivo conditions requires understanding whole-body absorption and regional P-gp activity.

Purpose of the Study:

  • To investigate the in vivo effect of verapamil, a P-gp inhibitor, on rhodamine123 (Rho123) absorption in different rat intestinal segments.
  • To determine regional differences in P-gp activity within the rat intestine.
  • To validate in vitro observations regarding P-gp inhibition and drug absorption in a whole-body context.

Main Methods:

  • Utilized an in situ loop method in rats to assess Rho123 absorption from the jejunum, ileum, and colon.

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  • Measured water movement within intestinal loops to correct for concentration changes.
  • Administered verapamil as a P-gp inhibitor and compared Rho123 clearance with and without the inhibitor.

    • Main Results:

    • Water movement varied regionally, being greatest in the colon and ileum.
    • Baseline Rho123 clearance followed the order: ileum > colon > jejunum.
    • Verapamil significantly increased Rho123 clearance in the jejunum and ileum, but not the colon.

    Conclusions:

    • P-gp actively inhibits drug absorption in the jejunum and ileum.
    • Significant regional differences in P-gp mediated drug absorption exist within the rat intestine.
    • These findings support the potential of P-gp inhibitors to enhance oral bioavailability of P-gp substrate drugs, particularly for jejunal and ileal absorption.