title: [Pharmacokinetic modelling of valproate in epileptic patients].
abstract: BACKGROUND
  The aim of our study was to develop and use a population pharmacokinetic model for assessment of individual valproate clearance in children and young adults suffering from epilepsy.
  
  
  METHODS
  The analysis was performed using 52 steady-state concentrations of valproate collected from 26 epileptic patients during the routine clinical practice in our hospital. The mean values of age and total body weight were 19.92 years and 57.12 kg, respectively. NONMEM software with ADVAN 1 subroutine was used for model building and assessing the influence of different covariates. A validation set of 20 epileptic patients (one blood sample per a patient) was used to estimate predicted performances of the pharmacokinetic model.
  
  
  RESULTS
  The typical mean value of the clearance of valproate estimated by the base model in our population was 0.3 77 I/h. Out of five considered covariates (total body weight, age, total daily dose, gender and polytherapy) only the age of the patients was a significant determinant of the clearance of valproate. The final regression model for the clearance of valproate was as following: CL (l/h) = 0.223 + 0.00819 * AGE CONCLUSION: The derived pharmacokinetical model describes the clearance of valproate in relation to patient's age in the observed population. it will help to improve the seizure control in young patients with epilepsy in Serbian population.
authors.affiliation: Medicinski fakultet Kragujevac, Katedra za farmakologiju i toksikologiju.
authors.forename: Mihajlo B
authors.initials: MB
authors.lastname: Jakovljević
authors.forename: Slobodan M
authors.initials: SM
authors.lastname: Janković
authors.forename: Natalija
authors.initials: N
authors.lastname: Todorović
authors.forename: Jasmina R
authors.initials: JR
authors.lastname: Milovanović
authors.forename: Snezana
authors.initials: S
authors.lastname: Janković
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D014635:Valproic Acid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid