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Related Experiment Videos

First-pass effect of morphine in rats

K Iwamoto, C D Klaassen

    The Journal of Pharmacology and Experimental Therapeutics
    |January 1, 1977
    PubMed
    Summary

    Morphine absorption is complete, but its bioavailability is significantly reduced by first-pass metabolism. Intestinal metabolism accounts for two-thirds of this effect, with the liver contributing the remainder.

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    Area of Science:

    • Pharmacokinetics
    • Drug Metabolism
    • Gastrointestinal Physiology

    Background:

    • The first-pass effect significantly impacts oral drug bioavailability.
    • Understanding morphine's first-pass metabolism is crucial for its therapeutic use.

    Purpose of the Study:

    • To quantify the first-pass effect of morphine in rats.
    • To differentiate the contributions of intestinal and hepatic metabolism to morphine's first-pass effect.

    Main Methods:

    • Pharmacokinetic analysis of 3H-morphine in Sprague-Dawley rats.
    • Comparison of plasma concentrations following oral, intravenous, and intraportal administration.
    • Measurement of cumulative urinary excretion of radioactivity.

    Main Results:

    • Morphine exhibited near-complete gastrointestinal absorption.
    • Oral and intraportal administration resulted in significantly reduced area under the plasma concentration-time curve (AUC) compared to intravenous administration.
    • The plasma half-life of unchanged morphine was unaffected by the route of administration.

    Conclusions:

    • Morphine undergoes substantial first-pass metabolism, with an overall reduction of 82% in bioavailability.
    • Intestinal extraction and/or metabolism contribute approximately two-thirds of the first-pass effect.
    • Hepatic metabolism accounts for the remaining one-third of morphine's first-pass effect.

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