Effect of single doses of sodium valproate on serum phenytoin level and protein binding in epileptic petients

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Abstract
Sodium valproate is a new antiepileptic with a wide spectrum of activity and low toxicity and is frequently used in combination with phenytoin. In order to clarify the interaction between the 2 drugs, the effect of single doses of sodium valproate on phenytoin steady-state serum concentration and protein binding was studied in patients with chronic epilepsy stabilized on phenytoin. The importance of performing protein binding interaction studies in vivo is underlined. Predictions from in vitro studies may be misleading because they may not take into account the kinetics of the drug in the whole animal. Probably the most important clinical implication of these findings is that total serum phenytoin levels may fall when sodium valproate is added to therapy and this may lead to an increase in dose under the mistaken belief that the effect of the drug has been reduced. Since it is the bound and not the free drug which is reduced, phenytoin intoxication may result from this action.

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