Pharmacokinetics of 10-OH-carbazepine, the main metabolite of the antiepileptic oxcarbazepine, from serum and saliva concentrations

Abstract

After administration of 600 mg of the antiepileptic oxcarbazepine to 7 healthy volunteers, serum and stimulated saliva samples were collected for the next 72 h. Concentrations of 10-OH-carbazepine, the main metabolite of oxcarbazepine, were determined by an HPLC method. The time-concentration curves showed a median Tmax of 8 h followed by a plateau until 24 h indicating saturable kinetic processes. Based on the curves, the pharmacokinetic parameters were calculated. The half-life of 10-OH-carbazepine in saliva, 13.8 +/- 3.7 (SD) h, was significantly shorter than in serum, 19.3 +/- 6.2 (SD) h. The half-life of 10-OH-carbazepine in serum was inversely correlated to the free fraction, estimated by the ratio saliva/serum concentrations. Calculation of free fraction by this method showed that 53.1 +/- 14.4 (SD) % of 10-OH-carbazepine is unbound in serum. There was a good correlation (r = 0.914) between serum and saliva concentrations of 10-OH-carbazepine from 8-72 h after administration of oxcarbazepine. This finding indicates that saliva concentrations may prove useful, as has been shown for carbamazepine, in therapeutic monitoring of oxcarbazepine treatment.