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Phenytoin-salicylate interaction

R F Leonard, P J Knott, G O Rankin

    Clinical Pharmacology and Therapeutics
    |January 1, 1981
    PubMed
    Summary
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    High-dose salicylate can displace phenytoin from protein binding, slightly increasing free phenytoin levels. However, this interaction is unlikely to be clinically significant, and phenytoin doses should not be altered solely based on salicylate therapy.

    Area of Science:

    • Pharmacology
    • Clinical Pharmacy

    Background:

    • Phenytoin is an anticonvulsant medication with a narrow therapeutic index.
    • Salicylates are commonly used analgesics and anti-inflammatory drugs.
    • Drug interactions involving protein binding displacement can affect medication efficacy and toxicity.

    Purpose of the Study:

    • To investigate the effect of increasing doses of salicylate on serum and salivary phenytoin concentrations in healthy adults.
    • To determine if salicylate causes clinically significant displacement of phenytoin from protein binding.

    Main Methods:

    • Ten healthy adults received daily phenytoin to reach therapeutic levels.
    • Subjects then took escalating doses of salicylate (325, 650, 975 mg) every 4 hours for 48 hours.
    • Serum and salivary phenytoin, and serum salicylate levels were monitored throughout the study.

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    Main Results:

    • Salicylate-induced protein binding displacement of phenytoin occurred only at the highest dose (975 mg).
    • At the highest dose, serum phenytoin decreased (13.5 to 10.3 µg/ml), salivary phenytoin increased (0.97 to 1.13 µg/ml), and the free fraction rose (7.14% to 10.66%).
    • No significant changes were observed at lower salicylate doses, and no direct correlation was found between salicylate and phenytoin concentrations.

    Conclusions:

    • High-dose salicylate can displace phenytoin from protein binding, leading to a modest increase in free phenytoin concentration.
    • This displacement is unlikely to be clinically significant, and routine adjustment of phenytoin dosage during salicylate therapy is not recommended unless toxicity is evident.