Plasma and cerebrospinal fluid pharmacokinetics of flurbiprofen in children.
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.
Kumpulainen
Elina
E
Department of Pharmacology and Toxicology, University of Eastern Finland, Kuopio.
Välitalo
Pyry
P
Kokki
Merja
M
Lehtonen
Marko
M
Hooker
Andrew
A
Ranta
Veli-Pekka
VP
Kokki
Hannu
H
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
D000700:Analgesics; D005480:Flurbiprofen