Title: Clinical Pharmacokinetics of Zanisamide and Drug Interaction with Other Anticonvulsants.
Abstract: Zonisamide (ZNS) is a useful anticonvulsant, but its pharmacokinetic properties are not sufficiently known. We discuss the optimal dosage regimen for ZNS by means of therapeutic drug monitoring (TDM). In our examination of whether the coadministration of other anticonvulsants might affect the serum concentration of ZNS, the following results were obtained: 1) a higher dosage of ZNS was required for the patients under 13 years old than for elderly patients to maintain the similar serum ZNS levels; 2) the serum protein binding rate of ZN.S was less than 40%, indicating serum levels of ZNS might unlikely be affected by coadministration of other protein-binding agents, although when ZNS was administered with valproic acid (VPA), both the binding rates of ZNS and VPA tended to decrease; 3) the serum concentrations linearly correlated with the doses when 10 mg/kg or less was given; 4) the serum ZNS concentration tended to decrease with coadministration of other anticonvulsants such as phenytoin, carbamazepine and phenobarbital, which are known to induce hepatic microsomal enzyme systems; and 5) thus TDM provides useful information on the appropriate dosage adjustments for ZNS.