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The effects of salicylate on the pharmacokinetics of phenytoin

From the Division of Neurology, Department of Medicine (Dr. Olanow), the Division of Family Medicine, Department of Community and Family Medicine (Dr. Finn), and the Department of Pharmacology (Dr. Prussak), Duke University Medical Center, Durham, NC.

The pharmacologic effect of a highly protein-bound drug is a function of the free serum concentration. In vitro studies have demonstrated that phenytoin is displaced from its protein-binding sites by acetylsalicylic acid. This resulted in increased concentrations of free serum phenytoin and raised the possibility of clinical toxicity. We have studied the effects of salicylates on six patients receiving long-term phenytoin therapy. This reduced the total serum phenytoin concentration but did not alter the free serum concentration. There was no loss of seizure control or toxicity. Total phenytoin concentrations in such patients may not accurately reflect pharmacologic activity and may be misleading.

Address correspondence and reprint requests to Dr. Olanow, P.O. Box 2905, Duke University Medical Center, Durham, NC 27710.

Accepted for publication May 21, 1980.