Fluctuations of 10-hydroxy-carbazepine during the day in epileptic patients.
Oxcarbazepine (OCBZ) is a new antiepileptic drug with a chemical structure similar to carbamazepine. We investigated the daily fluctuations of 10-OH-carbazepine (monohydroxy derivative, MHD), the clinically relevant metabolite of OCBZ, in patients with or without comedication. Twenty-two profiles of (total) serum concentrations of MHD from 18 epileptic patients on a b.i.d. OCBZ regimen were determined at 8.00, 11.00, 14.00, 17.00, 20.00 h (and 22.00 h/23.00 h). A patient was only considered twice if his comedication or OCBZ dosage had been changed. The maximal MHD concentrations were about 33% +/- 14% higher than the minimal MHD concentrations during the day. The free MHD concentrations were determined in 17 profiles. The mean free fraction of MHD was 56.7% +/- 5.5%. In combination with valproic acid the free fraction (64.0% +/- 1.4%) was slightly, but significantly higher (p < 0.05) than in monotherapy (52.3% +/- 0.9%) or in combination (58.0% +/- 2.6%) with other antiepileptic drugs (2 x phenobarbital, 2 x methsuximide, 1 x sulthiame). Further studies are necessary to clarify if the observed fluctuations of MHD are of clinical importance.
May
T W
TW
Department of Biochemistry, Gesellschaft für Epilepsieforschung e.V., Bethel, Bielefeld, Germany.
Rambeck
B
B
Sälke-Kellermann
A
A
D000293:Adolescent; D000328:Adult; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D008875:Middle Aged; D013997:Time Factors; D014635:Valproic Acid / Q000627:therapeutic use
C039775:10,11-dihydro-10-hydroxycarbamazepine; D002220:Carbamazepine; D014635:Valproic Acid