title: Oxcarbazepine extended-release formulation in epilepsy.
abstract: Oxcarbazepine (OXC) is a 10-keto-analogue of carbamazepine, which was developed and labeled as a follow-up antiepileptic drug, that was intended to overcome some of the pharmacological drawbacks of carbamazepine with similar efficacy. The main advantage is the nonoxidative metabolic pathway that allows a lower enzyme-induction profile and fewer drug interactions. OXC is rapidly and extensively reduced by cytosolic hepatic enzymes to its monohydroxylated derivative (MHD), thus OXC may be regarded as a prodrug with MHD representing the active antiepileptic agent. The immediate-release (IR) formulation of OXC (Trileptal(®), Timox(®)) has an almost complete bioavailibilty. It is rapidly absorbed and reaches peak concentrations after 1-3 h. MHD peak concentrations are measured within 4-12 h. Elimination half-life in healthy subjects is 1-5 h for OXC and 7-20 h for MHD. The OXC plasma concentration peak may have been responsible for side effects, such as dizziness, vertigo, coordination problems or blurred vision, which appeared more often with this formulation in individual cases than with the formulation available prior to 2000, or with another formulation that has been distributed in Scandinavian countries. Both possibilities offer a profile approaching the characteristics of an extended-release (ER) formulation. ER OXC was labeled in Germany in 2008 (Apydan(®) extent, Desitin Arzneimittel GmbH, Hamburg, Germany). Under steady-state conditions, Phase I studies show bioequivalence between IR and ER OXC. With ER OXC, OXC plasma peak concentrations and both OXC and MHD peak-trough fluctuations are markedly reduced. In clinical trials, comparisons between IR OXC twice daily versus ER OXC once daily failed to show significant differences; efficacy tended to be better with IR OXC, whereas OXC ER showed insignificant tolerability advantages. Another study is currently ongoing to compare the tolerability of both formulations under twice-daily administration conditions in patients with difficult-to-treat epilepsies who require a dosage increase of OXC and who are randomized to IR or ER OXC.
authors.affiliation: Epilepsiezentrum Kork, Landstr. 1, D-77694 Kehl-Kork, Germany. bsteinhoff@epilepsiezentrum.de.
authors.forename: Bernhard J
authors.initials: BJ
authors.lastname: Steinhoff