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Ticlopidine-theophylline interaction.

A Colli, G Buccino, M Cocciolo

    Clinical Pharmacology and Therapeutics
    |March 1, 1987
    PubMed
    Summary
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    Ticlopidine significantly alters theophylline metabolism, increasing its half-life and reducing clearance. These drug interaction effects are reversible after ticlopidine withdrawal, suggesting temporary liver enzyme inhibition.

    Area of Science:

    • Pharmacology
    • Drug Metabolism
    • Clinical Pharmacology

    Background:

    • Ticlopidine is an antithrombotic agent.
    • Theophylline is a bronchodilator.
    • Both drugs are primarily metabolized in the liver.

    Purpose of the Study:

    • To investigate potential pharmacokinetic interactions between ticlopidine and theophylline.
    • To assess the impact of ticlopidine on theophylline metabolism in healthy volunteers.

    Main Methods:

    • 10 healthy volunteers participated.
    • Theophylline pharmacokinetics were measured before, during (10 days), and after ticlopidine administration.
    • Pharmacokinetic parameters were re-evaluated 30 days after ticlopidine withdrawal and again 3 months later with placebo administration.

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    Main Results:

    • Ticlopidine administration significantly increased theophylline's elimination half-life (P < 0.001).
    • Total plasma clearance of theophylline was significantly reduced (P < 0.001) following ticlopidine treatment.
    • Theophylline pharmacokinetic parameters returned to baseline within 30 days of ticlopidine cessation.
    • No changes were observed with placebo administration.

    Conclusions:

    • Ticlopidine reversibly inhibits theophylline's liver metabolism.
    • The observed interaction does not appear to be due to direct liver toxicity.
    • This interaction highlights the importance of considering concomitant medication in patients using theophylline.