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Drug interactions of phenobarbital phenytoin valproic acid and carbamazepine

Drug interactions of phenobarbital phenytoin valproic acid and carbamazepine

Medical Journal of Kagoshima University 42(2): 159-175

Drug interactions of phenobarbital(PB), phenytoin(PHT), valproic acid(VPA) and carbamazepine(CBZ) with respect to total serum concentration and protein binding were studied. The following results were obtained. Serum concentration of PB increased when administered with PHT or VPA, and even more so when given with both PHT and VPA. PB and/or VPA had no effect on the serum concentration of PHT. Serum VPA concentration decreased when administered with PB or PHT, and more so when given with both PB and PHT. No variation could be found in protein binding when administering 2 or 3 of PB, PHT and VPA, although the free ratio of PHT increased by VPA. The serum concentration of CBZ decreased with PB or PHT, but not by VPA. CBZ failed to have any effect on the serum concentration of PB, but slightly decreased that of PHT and considerably that of VPA. The protein binding of CBZ was not influenced by PB, PHT or VPA, and that of PB, PHT and VPA was not influenced by CBZ. It is concluded from the results presented above that these four antiepileptic drugs, which have important clinical applications, induce complicated drug interactions when administered with each other. They should thus be given careful consideration for the safe and effective chemotherapy of epilepsy.

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