title: Population pharmacokinetics of lamotrigine in Chinese children with epilepsy.
abstract: OBJECTIVE
  To establish a population pharmacokinetics (PPK) model for lamotrigine (LTG) in Chinese children with epilepsy in order to formulate an individualized dosage guideline.
  
  
  METHODS
  LTG steady-state plasma concentration data from therapeutic drug monitoring (TDM) were collected retrospectively from 284 patients, with a total of 404 plasma drug concentrations. LTG concentrations were determined using a HPLC method. The patients were divided into 2 groups: PPK model group (n=116) and PPK valid group (n=168). A PPK model of LTG was established with NONMEM based on the data from PPK model group according to a one-compartment model with first order absorption and elimination. To validate the basic and final model, the plasma drug concentrations of the patients in PPK model group and PPK valid group were predicted by the two models.
  
  
  RESULTS
  The final regression model for LTG was as follows: CL (L/h)=1.01*(TBW/27.87)(0.635)*e(-0.753*VPA)*e(0.868*CBZ)*e(0.633*PB), Vd (L)= 16.7*(TBW/27.87). The final PPK model was demonstrated to be stable and effective in the prediction of serum LTG concentrations by an internal and external approach validation.
  
  
  CONCLUSIONS
  A PPK model of LTG in Chinese children with epilepsy was successfully established with NONMEM. LTG concentrations can be predicted accurately by this model. The model may be very useful for establishing initial LTG dosage guidelines.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Da-ke
authors.initials: DK
authors.lastname: He
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Jiong
authors.initials: J
authors.lastname: Qin
authors.forename: Shen
authors.initials: S
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Jian-ming
authors.initials: JM
authors.lastname: Zhang
authors.forename: Wei-qun
authors.initials: WQ
authors.lastname: Bao
authors.forename: Xiao-qing
authors.initials: XQ
authors.lastname: Song
authors.forename: Hai-tao
authors.initials: HT
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D044466:Asian People; D002648:Child; D002675:Child, Preschool; D002681:China; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007223:Infant; D000077213:Lamotrigine; D008297:Male; D008954:Models, Biological; D017711:Nonlinear Dynamics; D017410:Practice Guidelines as Topic; D012044:Regression Analysis; D012189:Retrospective Studies; D014227:Triazines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D000077213:Lamotrigine