Carbamazepine の薬物動態に関する検討 : 単独投与と Phenobarbital, Phenytoin, Sodium Valproate との併用の比較

概要

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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.
日本医療薬学会の論文
1996-02-10