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Related Experiment Videos

Cimetidine and ranitidine increase midazolam bioavailability.

J P Fee, P S Collier, P J Howard

    Clinical Pharmacology and Therapeutics
    |January 1, 1987
    PubMed
    Summary

    Ranitidine, like cimetidine, significantly increases midazolam bioavailability by reducing its metabolic clearance. This suggests ranitidine may also affect the metabolism of other drugs, impacting their efficacy and safety.

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    Area of Science:

    • Pharmacology
    • Drug Metabolism
    • Clinical Pharmacology

    Background:

    • Cimetidine is known to inhibit the oxidative metabolism of various drugs.
    • Emerging evidence suggests ranitidine may possess similar drug metabolism inhibitory properties.

    Purpose of the Study:

    • To investigate the effect of ranitidine, compared to cimetidine, on the pharmacokinetics of midazolam.
    • To determine if ranitidine alters midazolam absorption or hepatic clearance.

    Main Methods:

    • A within-subject crossover study involving eight healthy volunteers.
    • Administration of oral midazolam (15 mg) after pretreatment with cimetidine, ranitidine, or placebo.
    • Administration of intravenous midazolam (10 mg) on separate occasions for comparison.

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    Main Results:

    • Mean absolute bioavailability of oral midazolam increased by over 30% with cimetidine (P < 0.01).
    • Mean absolute bioavailability of oral midazolam increased by 26% with ranitidine (P < 0.05).
    • Increased bioavailability is attributed to reduced hepatic clearance, not enhanced absorption.

    Conclusions:

    • Ranitidine, similar to cimetidine, inhibits the metabolism of midazolam.
    • Reduced hepatic clearance is the primary mechanism for increased midazolam bioavailability.
    • Ranitidine may influence the metabolism and clinical effects of other co-administered drugs.