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Br J Clin Pharmacol. 2010 Oct;70(4):557-66. doi: 10.1111/j.1365-2125.2010.03720.x.

Plasma and cerebrospinal fluid pharmacokinetics of flurbiprofen in children.

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  • 1Department of Pharmacology and Toxicology, University of Eastern Finland, Kuopio.

Abstract

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 0.96l 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.

© 2010 The Authors. British Journal of Clinical Pharmacology © 2010 The British Pharmacological Society.

PMID:
20840447
[PubMed - indexed for MEDLINE]
PMCID:
PMC2950990
Free PMC Article
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