Variabilidad farmacocinética de oxcarbazepina en pacientes epilépticos / Pharmacokinetic variability of oxcarbazepine in epileptic patients

ABSTRACT

The aim of this study was to analyze the population pharmacokinetics of oxcarbazepine (OCBZ) measuring the serum level of its active metabolite, monohydroxylated oxcarbazepine (MHD). We studied a group of patients with symptomatic and cryptogenic epilepsy treated with OCBZ monotherapy orally, at least for 3 weeks. The mean doses, age and weight of the patients were 17.9 +/- 7.8 mg/kg/day, 35.6 +/- 16.4 years and 70.3 +/- 19.2 kg, respectively. Blood samples were taken before the first morning dose of OCBZ and MHD levels were determined by HPLC. A linear relationship was found between OCBZ dose and MHD serum level (r = 0.844, p < 0.001). The MHD serum concentration (mg/l) can be predicted as 0.85 x OCBZ dose (mg/kg). There was a significant correlation between observed and predicted MHD concentrations for each patient. The mean MHD clearance (Cl/F) calculated was 4.05 +/- 1.69 l/h, with a coefficient variation of 41%. It was independent of dose, age and weight and followed a non normal distribution. The half-life of MHD was 10.50 +/- 3.17 hours. The influence of other antiepileptic drugs on MHD pharmacokinetics was analyzed by comparing the Cl/F medians from groups of patients receiving concomitant drugs with OCBZ monotherapy group where no significant differences were found. The results can be used to estimate a priori OCBZ doses, in order to individualize the treatment.