THE NECESSITY OF ADJUSTING THE DOSAGE OF ZONISAMIDE WHEN COADMINISTERED WITH OTHER ANTIEPILEPTIC DRUGS

Zonisamide (ZNS), a new anti-epileptic drug that exhibits a wide anti- epileptic spectrum, is commonly prescribed concomitantly with other an ti-epileptic drugs. The interaction between ZNS and other anti-epilept ic drugs was investigated in epileptic patients, The steady state plas ma levels of all the anti-epileptic drugs were measured by high-perfor mance liquid chromatography. The concomitant administration of phenoba rbital (PB), phenytoin (PHT), or carbamazepine (CBZ) with ZNS signific antly decreased the ratio of the steady state plasma concentration to the administered dose (CID ratio) of ZNS, whereas clonazepam (CZP) and valproic acid (VPA) when administered concomitantly with ZNS did not change the CID ratio, Significant negative correlations were observed between the CID ratio of ZNS and the doses of PB, PHT, CBZ, and VPA. O n the other hand, the ratio of the plasma concentration of carbamazepi ne-10,11-epoxide (CBZ-E), the major active metabolite of CBZ, to the p lasma concentration of CBZ was significantly decreased bg concomitant administration with ZNS, indicating that ZNS inhibits; the metabolism of CBZ. These findings show that when ZNS is administered concomitantl y with these anti-epileptic drugs, it is necessary to monitor the plas ma concentration of ZNS in order to adjust its dosage.