Plasma and cerebrospinal fluid pharmacokinetics of flurbiprofen in children

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTFlurbiprofen is a commonly used non‐steroidal anti‐inflammatory drug in children to treat pain and fever. There is limited information on the pharmacokinetics of flurbiprofen in children and no data on the cerebrospinal fluid permeation of flurbiprofen.WHAT THIS STUDY ADDSOur population pharmacokinetic model indicates that weight‐based dosing of flurbiprofen is appropriate in children older than 6 months. The bioavailability of oral flurbiprofen syrup is high, 71–91%, and thus, the oral syrup provides accurate dosing in paediatric patients. Cerebrospinal fluid concentrations of flurbiprofen are markedly higher than the unbound plasma concentrations.AIMSThis study was designed to characterize paediatric pharmacokinetics and central nervous system exposure of flurbiprofen.METHODSThe 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.RESULTSFlurbiprofen 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 0.96 l 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 (Vss) was 8.1 l 70 kg−1. Flurbiprofen permeated into the CSF, reaching concentrations that were seven‐fold higher compared with unbound plasma concentrations.CONCLUSIONSFlurbiprofen pharmacokinetics can be described using only weight as a covariate in children above 6 months, while more research is needed in neonates and in younger infants.