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The influence of co-medication with zonisamide (ZNS) on the serum concentration and protein binding of phenytoin (PHT) and sodium valproate (VPA) was studied in 21 pediatric patients. No significant correlation between the daily ZNS dose, and total serum concentrations, free concentrations or free fractions (FF) of PHT or VPA was observed. The patient study showed that changes in the FF of PHT and VPA were correlated more closely with the serum protein and bilirubin levels than changes in the ZNS dosage. An in vitro study revealed that the addition of ZNS caused decreases in the FF of PHT and VPA. However, these decreases were within the range of measurement error and were negligible. In conclusion, no significant effect of ZNS on the serum concentration or protein binding of PHT or VPA was demonstrated.
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