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Related Experiment Videos

Interaction between diflunisal and warfarin

M J Serlin, S Mossman, R G Sibeon

    Clinical Pharmacology and Therapeutics
    |October 1, 1980
    PubMed
    Summary
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    Diflunisal increased unbound warfarin but did not change anticoagulant response in healthy men. Upon discontinuation, warfarin levels and anticoagulant effect returned to baseline at different rates, indicating complex drug interactions.

    Area of Science:

    • Pharmacology
    • Drug Metabolism
    • Clinical Pharmacokinetics

    Background:

    • Warfarin is a widely used anticoagulant.
    • Understanding drug interactions with warfarin is crucial for patient safety.
    • Diflunisal is a nonsteroidal anti-inflammatory drug.

    Purpose of the Study:

    • To investigate the effects of diflunisal on the pharmacokinetics and pharmacodynamics of warfarin.
    • To assess how diflunisal influences warfarin protein binding and anticoagulant activity.

    Main Methods:

    • Five healthy male subjects received subtherapeutic doses of warfarin.
    • Diflunisal (500 mg twice daily) was administered for two weeks.
    • Measurements included total and unbound warfarin concentrations, and prothrombin complex activity (PCA).

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    Main Results:

    • Diflunisal increased the percentage of unbound warfarin (from 1.02% to 1.24%) and decreased total warfarin levels (from 741 to 533 ng/ml).
    • No significant alteration in anticoagulant response (PCA) was observed during diflunisal co-administration.
    • Following diflunisal discontinuation, warfarin's anticoagulant effect diminished, with unbound and total warfarin concentrations returning to baseline at different rates.

    Conclusions:

    • Diflunisal alters warfarin protein binding and disposition kinetics without affecting the immediate anticoagulant response.
    • The observed differences in the rate of return to baseline suggest complex interactions affecting warfarin's elimination or protein binding.
    • These findings highlight the importance of monitoring warfarin therapy when co-administered with NSAIDs like diflunisal.