Effects of Zonisamide on Serum Levels of Phenytoin and Carbamazepine

Abstract

In order to study the effects of zonisamide (ZNS) on serum levesl of phenytoin (PHT) and carbamazepine (CBZ). PHT and CBZ levels were determined in 17 cases before and after changes in ZNS dose. Drug compliance was good in all subjects. Diurnal variations of PHT and CBZ were determined in one case, and a clear increase in PHT levels and no change in CBZ levels, after ZNS dose increase, were obtained. Lassitude, sleepiness, ataxia, nystagmus and dysarthria observed in this case were ascribable to the increased level of PHT which was caused by an increase of ZNS dose.
PHT levels increased significantly after comedication or increase of ZNS while increase of CBZ levels failed to reach statistically significant level.
To eliminate the effect of one hour difference in sampling time changes in serum levels were recorded only when more than 25% of change in PHT or CBZ levels in comparison with those before ZNS dose change was observed. Based on this criteria, ZNS increased PHT levels in 40% of subjects and decreased in 10% of subjects. ZNS increased CBZ levels in 29. 4% of subjects.
This study, therefore, indicates that the determinations of PHT and CBZ levels are needed when ZNS is to be coadiministered or ZNS dose to be changed.