title: Plasma and cerebrospinal fluid pharmacokinetics of flurbiprofen in children.
abstract: OBJECTIVE
  This study was designed to characterize paediatric pharmacokinetics and central nervous system exposure of flurbiprofen.
  
  
  METHODS
  The pharmacokinetics of flurbiprofen were studied in 64 healthy children aged 3 months to 13 years, undergoing surgery with spinal anaesthesia. Children were administered preoperatively a single dose of flurbiprofen intravenously as prodrug (n= 27) or by mouth as syrup (n= 37). A single cerebrospinal fluid (CSF) sample (n= 60) was collected at the induction of anaesthesia, and plasma samples (n= 304) before, during and after the operation (up to 20 h after administration). A population pharmacokinetic model was built using the NONMEM software package.
  
  
  RESULTS
  Flurbiprofen concentrations in plasma were well described by a three compartment model. The apparent bioavailability of oral flurbiprofen syrup was 81%. The estimated clearance (CL) was 0.96l h(-1) 70 kg(-1) . Age did not affect the clearance after weight had been included as a covariate. The estimated volume of distribution at steady state (V(ss) ) was 8.1 l 70 kg(-1) . Flurbiprofen permeated into the CSF, reaching concentrations that were seven-fold higher compared with unbound plasma concentrations.
  
  
  CONCLUSIONS
  Flurbiprofen pharmacokinetics can be described using only weight as a covariate in children above 6months, while more research is needed in neonates and in younger infants.
authors.affiliation: Department of Pharmacology and Toxicology, University of Eastern Finland, Kuopio.
authors.forename: Elina
authors.initials: E
authors.lastname: Kumpulainen
authors.forename: Pyry
authors.initials: P
authors.lastname: Välitalo
authors.forename: Merja
authors.initials: M
authors.lastname: Kokki
authors.forename: Marko
authors.initials: M
authors.lastname: Lehtonen
authors.forename: Andrew
authors.initials: A
authors.lastname: Hooker
authors.forename: Veli-Pekka
authors.initials: VP
authors.lastname: Ranta
authors.forename: Hannu
authors.initials: H
authors.lastname: Kokki
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000700:Analgesics / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D005260:Female; D005480:Flurbiprofen / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D006801:Humans; D007223:Infant; D007275:Injections, Intravenous; D008297:Male; D008954:Models, Biological
chemical_list: D000700:Analgesics; D005480:Flurbiprofen