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Cimetidine interaction with amitriptyline.

S H Curry, C L DeVane, M M Wolfe

    European Journal of Clinical Pharmacology
    |January 1, 1985
    PubMed
    Summary
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    Cimetidine significantly alters the metabolism of amitriptyline, increasing its plasma levels while decreasing nortriptyline. These drug interactions affect physiological responses and subjective experiences.

    Area of Science:

    • Pharmacology
    • Clinical Pharmacy
    • Drug Interactions

    Background:

    • Amitriptyline is a widely prescribed tricyclic antidepressant.
    • Cimetidine is a common medication used to reduce stomach acid.
    • Potential drug interactions between these medications require investigation.

    Purpose of the Study:

    • To investigate the pharmacokinetic and pharmacodynamic interactions between cimetidine and amitriptyline.
    • To assess the impact of cimetidine on amitriptyline and nortriptyline plasma concentrations.
    • To evaluate the clinical effects of this interaction on physiological and subjective measures.

    Main Methods:

    • Plasma concentrations of amitriptyline and its active metabolite, nortriptyline, were measured.
    • Standing blood pressure and pulse rate were monitored.

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  • Cognitive function was assessed using the Digit Symbol Substitution Test.
  • Subjective effects were evaluated using visual analogue scales.

    • Main Results:

    • Cimetidine administration led to increased plasma concentrations of amitriptyline.
    • Cimetidine decreased plasma concentrations of nortriptyline, suggesting inhibition of presystemic metabolism.
    • Changes in blood pressure, pulse rate, and cognitive function correlated with amitriptyline levels.
    • Subjective ratings of drug effects correlated with nortriptyline plasma concentrations.

    Conclusions:

    • Cimetidine inhibits the metabolism of amitriptyline, leading to higher plasma levels of the parent drug.
    • The observed changes in physiological and subjective effects are linked to altered plasma concentrations of amitriptyline and nortriptyline.
    • This interaction highlights the importance of considering concomitant medication use in patients taking amitriptyline.