INTERACTION BETWEEN VALPROATE FORMULATION AND PHENYTOIN CONCENTRATIONS

Changes in phenytoin concentrations caused by switching valproate form ulations with different absorption rates were retrospectively investig ated in eleven epileptic patients receiving treatment with both drugs. Total plasma phenytoin concentrations were measured before and after a standard tablet of valproate was replaced by the same dose as a slow -release tablet. The mean plasma phenytoin level rose significantly fr om 14.4 to 18.7 mu g . ml(-1). Nine of eleven patients had markedly in creased phenytoin levels (by 21 to 72 %), and two developed toxic symp toms. The results indicate that changing valproate formulations can ca use major alterations in the plasma concentration of co-administered p henytoin.