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Related Experiment Videos

Cimetidine interaction with imipramine and nortriptyline.

S A Henauer, L E Hollister

    Clinical Pharmacology and Therapeutics
    |February 1, 1984
    PubMed
    Summary

    Cimetidine increased imipramine bioavailability but not nortriptyline. Individual responses to this drug interaction varied, highlighting the need for monitoring tricyclic antidepressant levels.

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    Area of Science:

    • Pharmacology
    • Drug Metabolism
    • Clinical Pharmacy

    Background:

    • Cimetidine is known to inhibit cytochrome P450 enzymes involved in drug metabolism.
    • Tricyclic antidepressants (TCAs) like imipramine and nortriptyline are metabolized via distinct pathways, including demethylation and hydroxylation.
    • Interactions between cimetidine and TCAs can alter drug bioavailability and clearance.

    Purpose of the Study:

    • To investigate the pharmacokinetic interaction between cimetidine and two tricyclic antidepressants, imipramine and nortriptyline, in healthy subjects.
    • To determine the effect of cimetidine on the bioavailability and clearance of imipramine and its active metabolite, desipramine.
    • To assess the impact of cimetidine on the pharmacokinetics of nortriptyline and its 10-hydroxy metabolite.

    Main Methods:

    • Healthy subjects received cimetidine pretreatment.
    • Pharmacokinetic parameters of imipramine, desipramine, nortriptyline, and its 10-hydroxy metabolite were measured.
    • Comparison of drug levels and metabolic profiles with and without cimetidine.

    Main Results:

    • Cimetidine significantly increased imipramine bioavailability and decreased its clearance.
    • Nortriptyline bioavailability was not significantly altered by cimetidine.
    • The bioavailability of the 10-hydroxy metabolite of nortriptyline was unexpectedly increased by cimetidine.
    • Significant inter-individual variability was observed in the pharmacokinetic changes.

    Conclusions:

    • Cimetidine's interaction with TCAs is complex and pathway-dependent, affecting imipramine and nortriptyline differently.
    • The unpredictable nature of these interactions and individual variability underscore the potential for TCA toxicity.
    • Monitoring plasma concentrations of TCAs is recommended when co-administered with cimetidine to ensure patient safety.

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