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Plasma and cerebrospinal fluid pharmacokinetics of flurbiprofen in children
Author(s) -
Kumpulainen Elina,
Välitalo Pyry,
Kokki Merja,
Lehtonen Marko,
Hooker Andrew,
Ranta VeliPekka,
Kokki Hannu
Publication year - 2010
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2010.03720.x
Subject(s) - flurbiprofen , pharmacokinetics , medicine , nonmem , cerebrospinal fluid , pharmacology , bioavailability , population , anesthesia , volume of distribution , dosing , environmental health
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Flurbiprofen 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 ADDS Our 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. AIMS 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 0.96 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 ( 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 6 months, while more research is needed in neonates and in younger infants.