Pharmacokinetics of oxcarbazepine in the dog

Oxcarbazepine has been proven to be a promising new antiepileptic drug for the treatment of human epilepsy. Unlike carbamazepine, it is not oxidatively metabolized in humans, and therefore causes almost no induction of hepatic enzymes at clinically effective dosages. Though showing similar efficacy to carbamazepine, it has been reported to cause significantly fewer side-effects. It was the purpose of the present study to determine whether oxcarbazepine might be suitable for the treatment of canine epilepsy. In single-dose experiments, 40 mg/kg oxcarbazepine as a suspension was administered to seven dogs via gastric tube. Plasma concentrations reached peak concentrations of 2.4-8.8 micrograms/mliter at about 1.5 h and declined with an elimination half-life of approximately 4 h. The corresponding concentrations of its metabolite, 10,11-dihydro-10-hydroxycarbamazepine, did not exceed 1 micrograms/mliter. During continued treatment for 8 days, doses of 30 and 50 mg/kg were administered orally in capsules to two dogs three times a day. Plasma concentrations showed a pronounced decline from day 3, and the terminal half-life decreased to 2 h and 1 h. This is considered to be the result of oxcarbazepine inducing its own metabolism. The data reveal that oxcarbazepine, compared with former results with carbamazepine, offers no advantage for the treatment of epileptic dogs.