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Related Experiment Videos

Surface activity and concentration dependent intestinal permeability in the rat

A Lindahl1, B Persson, A L Ungell

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

Pharmaceutical Research
|February 9, 1999
PubMed
Summary

Drug surface activity significantly impacts intestinal drug absorption. Fluvastatin and verapamil

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Area of Science:

  • Pharmacology
  • Physical Chemistry

Background:

  • Intestinal drug absorption is influenced by various physicochemical properties.
  • Understanding drug effective permeability (P(eff)) is crucial for predicting in vivo drug behavior.
  • Surface activity of drugs can affect their interaction with biological membranes.

Purpose of the Study:

  • To investigate the relationship between intestinal effective permeability (P(eff)) and the surface activity of fluvastatin and verapamil.
  • To determine if a drug's inherent surface activity influences its absorption characteristics.

Main Methods:

  • In situ rat colon perfusions were used to determine P(eff) values for fluvastatin, antipyrine, and D-glucose.
  • Perfusion solutions varied in drug concentrations and surface tension, with ethyl-(hydroxyethyl) cellulose (EHEC) used to reduce surface tension.

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  • P(eff) values for verapamil were correlated with surface tension data from existing literature.

    • Main Results:

    • Fluvastatin's P(eff) showed an inverse correlation with perfusion solution surface tension below the critical micelle concentration (CMC).
    • Reducing surface tension with EHEC significantly increased fluvastatin's P(eff) by 36% and antipyrine's by 49%, but not D-glucose's.
    • Verapamil's P(eff) also correlated inversely with surface tension.

    Conclusions:

    • The surface activity of fluvastatin contributes to its concentration-dependent colonic P(eff).
    • Drug molecule surface activity is a critical physicochemical factor in evaluating drug absorption studies.
    • These findings highlight the importance of considering drug surface properties in in vitro and in situ absorption assessments.