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Related Experiment Videos

Diazepam-cimetidine drug interaction: a clinically significant effect.

R L Ruffalo, J F Thompson, J L Segal

    Southern Medical Journal
    |September 1, 1981
    PubMed
    Summary

    Cimetidine inhibits metabolism of certain benzodiazepines like diazepam, increasing sedation. Oxazepam and lorazepam are safer alternatives as they bypass this drug interaction pathway.

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    Area of Science:

    • Pharmacology
    • Drug Metabolism
    • Drug Interactions

    Background:

    • Cimetidine is known to inhibit liver microsomal metabolism.
    • Many benzodiazepines, such as diazepam and chlordiazepoxide, are metabolized by the cytochrome P450 oxidase system.
    • This interaction leads to increased drug half-life and reduced clearance, potentially causing enhanced sedation.

    Purpose of the Study:

    • To investigate the interaction between cimetidine and various benzodiazepines.
    • To identify benzodiazepines that can be safely co-administered with cimetidine.
    • To understand the metabolic pathways involved in benzodiazepine-cimetidine drug interactions.

    Main Methods:

    • Review of existing literature on drug metabolism and interactions.
    • Analysis of metabolic pathways for different benzodiazepines (cytochrome P450 vs. glucuronidation).

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  • Comparison of pharmacokinetic changes in benzodiazepines when co-administered with cimetidine.

    • Main Results:

    • Cimetidine inhibits the metabolism of diazepam and chlordiazepoxide via cytochrome P450.
    • This inhibition results in a longer half-life and decreased clearance of these drugs.
    • Oxazepam and lorazepam are metabolized by glucuronidation, bypassing the cytochrome P450 pathway and cimetidine's inhibitory effects.

    Conclusions:

    • Cimetidine significantly interacts with benzodiazepines metabolized by cytochrome P450.
    • Oxazepam and lorazepam are not subject to metabolic inhibition by cimetidine.
    • Oxazepam and lorazepam are recommended as preferred benzodiazepines when co-administration with cimetidine is clinically necessary.