Pharmacokinetic interactions of the new antiepileptic drugs

Therapy with traditional antiepileptic drugs is associated with a wide range of pharmacokinetic drug-drug interactions. In particular, enzyme induction, enzyme inhibition and displacement from protein binding may result in important changes in serum concentrations of antiepileptics. Relevant interactions have also been described for some new antiepileptics. Felbamate increases serum concentrations of phenytoin, phenobarbital and valproic acid (sodium valproate). On the other hand, it reduces concentrations of carbamazepine and increases concentrations of its metabolite carbamazepine-10,11-epoxide. Concentrations of felbamate itself are reduced by phenytoin and carbamazepine. Concentrations of lamotrigine are considerably increased by valproic acid and decreased by phenytoin, carbamazepine and phenobarbital (phenobarbitone). Vigabatrin reduces serum concentrations of phenytoin by approximately 20%. On the other hand, some new antiepileptics have the important advantage of not interfering with the metabolism of other antiepileptics; this is the case for gabapentin, lamotrigine and oxcarbazepine. Furthermore, the pharmacokinetics of gabapentin, oxcarbazepine and vigabatrin are independent of concomitant drugs. These aspects are especially important as, until now, new antiepileptics have been most often utilised as add-on therapy.