The clinical pharmacokinetics of the new antiepileptic drugs

Because pharmacokinetics is a major determinant of the magnitude and durati on of pharmacologic response, understanding the kinetic properties of the n ew antiepileptic drugs (AEDs) is essential for the correct use of these com pounds in clinical practice. After oral administration, absorption is rapid and relatively efficient for the new AEDs, the most notable exception bein g gabapentin, whose bioavailability decreases with increasing dosage. None of the new AEDs is extensively bound to plasma proteins except for tiagabin e, which is over 95% protein-bound. The route of elimination differs to an important extent from one compound to another, and elimination half-lives r ange from over 30 h for zonisamide to 5-7 h for gabapentin. For all drugs t hat are metabolized, half-life is shortened and clearance is increased when patients receive concomitant enzyme-inducing agents such as barbiturates, phenytoin, and carbamazepine. Lamotrigine metabolism is markedly inhibited by valproic acid, and felbamate may increase the serum levels of most other AEDs. Felbamate, topiramate, and oxcarbazepine may also reduce the efficac y of the contraceptive pill by stimulating its metabolism.