First dose and steady-state pharmacokinetics of oxcarbazepine and its 10-hydroxy metabolite.
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.
Dickinson
R G
RG
Department of Medicine, University of Queensland, Brisbane, Australia.
Hooper
W D
WD
Dunstan
P R
PR
Eadie
M J
MJ
D000328:Adult; D000927:Anticonvulsants / Q000493:pharmacokinetics*; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D000078330:Oxcarbazepine
C039775:10,11-dihydro-10-hydroxycarbamazepine; D000927:Anticonvulsants; D002220:Carbamazepine; D000078330:Oxcarbazepine