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The plasma concentrations of carbamazepine (CBZ) and its metabolites, CBZ-10, 11-epoxide (CBZ-E) and 10, 11-dihydro-CBZ-trans-diol (CBZ-T) were measured by HPLC in 81 epileptic patients treated with CBZ alone and with other anticonvulsants, such as phenytoin (PHT), phenobarbital (PB) and sodium valproate (VPA). The following results were obtained. First, the plasma concentration of CBZ decreased, while those of CBZ-E and CBZ-T inversely tended to increase, when it was given together with other anticonvulsants such as PHT and/or PB that induced liver microsomal enzymes. The dose of CBZ in combination therapy with PHT and/or PB was required to be higher than in CBZ monotherapy to maintain the same plasma concentration. Second, when CBZ was given with VPA, the plasma of CBZ-E/CBZ ratio increased, while that of CBZ-T/CBZ-E ratio decreased. This suggests that VPA decreases CBZ-E clearance. Third, this study suggests that the dose of CBZ could be increased to maintain the optimal plasma concentration when it was given with PHT and/or PB. On the other hand, an abnormal elevation of CBZ-E should be noted when CBZ was given with VPA, as there is a possibility that VPA decreases CBZ-E clearance.

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Pharmacokinetics of Carbamazepine and its Metabolites in Combination Therapy. Carbamazepine Compared Monotherapy with its Combination Therapy of Phenobarbital, Phenytoin, Sodium Valproate.