Plasma and cerebrospinal fluid pharmacokinetics of flurbiprofen in children |
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Authors: | Elina Kumpulainen Pyry V?litalo Merja Kokki Marko Lehtonen Andrew Hooker Veli-Pekka Ranta Hannu Kokki |
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Affiliation: | 1Department of Pharmacology and Toxicology, University of Eastern Finland, Kuopio;2Department of Anaesthesiology and Intensive Care, Kuopio University Hospital, Kuopio;3Department of Pharmaceutics, University of Eastern Finland, Kuopio;4Department of Pharmaceutical Chemistry, University of Eastern Finland, Kuopio, Finland;5Department of Pharmaceutical Biosciences, University of Uppsala, Uppsala, Sweden |
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Abstract: | 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. |
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Keywords: | cerebrospinal fluid children flurbiprofen NONMEM pain population pharmacokinetics |
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