title: Population pharmacokinetics of oxcarbazepine active metabolite in Chinese children with epilepsy.
abstract: OBJECTIVE
  This study was to establish the population pharmacokinetic (PPK) model of pharmacologically active metabolite of oxcarbazepine (OXC) and to estimate PPK parameters for the optimal individuation administration of OXC in Chinese children with epilepsy.
  
  
  METHODS
  The pharmacologically active metabolite, 10-monohydroxy derivative of OXC (MHD)was used as the analytical target for monitoring therapy of OXC. A total of 840 MHD serum samples from 466 children with epilepsy were analyzed using high-performance liquid chromatography with UV detection. Patients' clinical data were retrospectively collected. Population pharmacokinetics analysis was performed using a non-linear mixed-effect model with Phoenix NLME 1.2. Pharmacokinetic parameters were estimated according to a one-compartment model with first-order absorption and elimination. Effects of age,gender, total body weight (TBW), daily doseper weight (DDPW) and use of concomitant antiepileptic drugs (AEDs) were analyzed.Bootstrap and predictive check were used simultaneously to validate the final population pharmacokinetics models.
  
  
  RESULTS
  The final PPK model of MHD was: Ka = 0.645 h⁻¹, V(L) = (11.3 + (age - 90.5) x 0.0282 + (TBW - 25.0) x 0.402) x e(0.0689), CL (L/h) = (0.557 + (DDPW - 20.8) x 0.00367 + (gender) x (-0.0636)) x e(0.120). The final PPK model was demonstrated to be suitable and effective by the bootstrap and predictive check.
  
  
  CONCLUSIONS
  A PPK model of MHD in Chinese children with epilepsy was successfully established. PPK parameters of MHD could be predicted accurately by this model. This model may be very useful for establishing individual dosage guidelines of OXC in Chinese children with epilepsy.
authors.forename: Jing
authors.initials: J
authors.lastname: Peng
authors.forename: Hua-Nian
authors.initials: HN
authors.lastname: Zhang
authors.forename: Zhi-Sheng
authors.initials: ZS
authors.lastname: Liu
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000627:therapeutic use; D044466:Asian People; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008954:Models, Biological; D017711:Nonlinear Dynamics; D000078330:Oxcarbazepine; D012189:Retrospective Studies
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine; D000078330:Oxcarbazepine