[Pharmacokinetic variability of oxcarbazepine in epileptic patients].
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.
Viola
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MS
Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina. msviola@huemul.ffyb.uba.ar
Bercellini
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Saidón
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Rubio
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D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002220:Carbamazepine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000078330:Oxcarbazepine
D000927:Anticonvulsants; D002220:Carbamazepine; D000078330:Oxcarbazepine