Influence of the combined treatment with phenytoin or valproate on serum concentration of carbamazepine

To clarify the pharmacokinetic interaction in poly-therapy for epilepsy, the serum concentration of carbamazepine (CZB) was measured in epileptic patients to whom CBZ had been prescribed chronically with or without phenytoin (PHT) and sodium valproate (VPA). The serum CBZ concentrations increased with increasing doses of CBZ, but increased less at higher doses. Chiliren (<12 yrs) showed lower serum CBZ concentrations than patients 12 years old and older. The L/D ratios (L : CBZ level, D : dose/body weight) were significantly decreased by the combined treatment with PHT and VPA in a dose-dependent manner, probably due to an induction of metabolizing enzyme. These findings suggest that especially in the case of change of the drug therapy from mono-therapy to mono therapy, careful monitoring of serum concentration is necessary.

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