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 × phenobarbital, 2 × methsuximide, 1 × sulthiame). Further studies are necessary to clarify if the observed fluctuations of MHD are of clinical importance.