First dose and steady-state pharmacokinetics of oxcarbazepine and its 10-hydroxy metabolite

Abstract

Summary The pharmacokinetics of oxcarbazepine (a new anticonvulsant which is a congener of carbamazepine) and of its 10-hydroxy metabolite were studied at the outset of therapy in 8 adult epileptics comedicated with other anticonvulsants. The pharmacokinetic study was repeated under steady-state conditions after 3 months of drug intake in 6 of these subjects. The plasma elimination half-life of oxcarbazepine appeared to lie in the range 1.0–2.5 h, and that of its 10-hydroxy metabolite averaged 8.4 h. The apparent oral clearance of the parent drug (averaging 2.51·kg⁻¹·h⁻¹) was high enough to suggest substantial presystemic elimination. The oral clearance fell after 3 months of drug intake, but the half-lives of the drug and metabolite showed no statistically significant change over this time. Steady-state plasma levels of both drug and metabolite were linearly related to drug dose, metabolite levels averaging 9 times those of the parent substance.