Plasma and cerebrospinal fluid pharmacokinetics of flurbiprofen in children
Elina Kumpulainen1, Pyry Välitalo, Merja Kokki
1Department of Pharmacology and Toxicology, University of Eastern Finland, Kuopio.
Insights
This study characterized flurbiprofen pharmacokinetics in children, finding weight is a key factor for dosing. Flurbiprofen effectively crosses into the central nervous system (CNS) for pain management.
Area of Science:
- Pharmacology
- Pediatric Anesthesiology
- Drug Metabolism
Background:
- Flurbiprofen is a non-steroidal anti-inflammatory drug (NSAID) used for pain management.
- Understanding its pharmacokinetic profile in children is crucial for safe and effective dosing.
Purpose of the Study:
- To characterize the pharmacokinetics of flurbiprofen in pediatric patients.
- To assess central nervous system (CNS) exposure to flurbiprofen in children.
Main Methods:
- Population pharmacokinetic modeling using NONMEM in 64 healthy children (3 months to 13 years).
- Administration of single-dose flurbiprofen intravenously or orally.
- Collection of plasma and cerebrospinal fluid (CSF) samples over 20 hours post-administration.
Main Results:
- Oral flurbiprofen bioavailability was 81% with a clearance of 0.96 L/h/70kg.
- Weight was the primary covariate influencing pharmacokinetics; age had no significant effect in children over 6 months.
- Flurbiprofen achieved high concentrations in CSF, sevenfold higher than unbound plasma levels.
Conclusions:
- Flurbiprofen pharmacokinetics in children over 6 months can be predicted using weight as a covariate.
- Further research is needed for neonates and younger infants to optimize dosing.
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.
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