title: Population pharmacokinetic analysis for 10-monohydroxy derivative of oxcarbazepine in pediatric epileptic patients shows no difference between Japanese and other ethnicities.
abstract: Oxcarbazepine is an anti-epileptic drug, which is almost completely metabolized by cytosolic enzymes in the liver to the active 10-monohyroxy metabolite (MHD) following oral administration. The pharmacokinetic (PK) profiles of MHD were evaluated in pediatric epileptic patients and a possible ethnic difference in PK of MHD between Japanese and non-Japanese pediatric patients was assessed. A non-linear mixed effect modeling approach was used to determine the PK of MHD. A one-compartment population model with first-order absorption appropriately described the PK of MHD. No clinically relevant differences were found for using body surface area or weight to explain between-patient variability, therefore the final model included the effects of body weight on apparent clearance (CL/F) and apparent volume of distribution (V/F) of MHD, and in addition, the effect of 3 concomitant anti-epileptic drugs (carbamazepine, phenobarbital and phenytoin) on CL/F of MHD. Inclusion of ethnicity as a covariate in the final model, concluded no ethnic difference with respect to CL/F of MHD between Japanese and non-Japanese patients. Hence, oxcarbazepine can be generally applied using the same dosage and administration for the treatment of partial onset seizures in pediatric patients, regardless of ethnicity.
authors.affiliation: Drug Metabolism and Pharmacokinetics, Novartis Pharma K.K., Tokyo, Japan; Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan. Electronic address: ikuo.sugiyama@novartis.com.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Sugiyama
authors.affiliation: Integrated Quantitative Sciences, Novartis Pharma AG, Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bouillon
authors.affiliation: Drug Metabolism and Pharmacokinetics, Novartis Pharma K.K., Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Drug Metabolism and Pharmacokinetics, Novartis Pharma K.K., Tokyo, Japan.
authors.forename: Hikoe
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirota
authors.affiliation: Integrated Quantitative Sciences, Novartis Pharma AG, Basel, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Fink
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000367:Age Factors; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D044466:Asian People; D001711:Biotransformation; D001835:Body Weight; D002220:Carbamazepine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000208:ethnology; D005260:Female; D065569:Gastrointestinal Absorption; D006801:Humans; D006900:Hydroxylation; D007564:Japan; D008297:Male; D008954:Models, Biological; D017711:Nonlinear Dynamics
chemical_list: D000927:Anticonvulsants; C476610:oxcarbamazepine; D002220:Carbamazepine
keywords: Epilepsy; Ethnic sensitivity assessment; Japanese population; Oxcarbazepine; Pediatrics; Population PK