OBJECTIVE: The purpose of this study was to evaluate the cerebrospinal fluid (CSF) distribution of an NSAID, ketoprofen, in children. Ketoprofen concentrations were determined from the CSF, plasma and protein-free plasma samples. METHODS: Children (n = 21), aged 13-94 months, were given intravenous ketoprofen (1 mg/kg) prior to surgery under spinal anaesthesia. Single venous blood and CSF samples from each patient were collected simultaneously 7-67 minutes after the drug administration. Ketoprofen concentrations in the samples were determined using gas chromatography-mass spectrometry. RESULTS: Ketoprofen entered the CSF and was detectable in all samples. However, CSF delivery was limited; the ratio of ketoprofen concentration in CSF to plasma remained below 0.006 at all times. Ketoprofen was highly bound (> 98%) to plasma proteins. The free ketoprofen fraction was not in equilibrium with the CSF, and no clear peak drug concentration in the CSF was observed. CONCLUSION: This study shows that ketoprofen is able to enter the CSF of children, which enables central analgesic effects of ketoprofen. However, the slow distribution of ketoprofen into the CSF and the apparently low absolute concentrations has to be taken into account when central analgesic effects are desired.
OBJECTIVE: The purpose of this study was to evaluate the cerebrospinal fluid (CSF) distribution of an NSAID, ketoprofen, in children. Ketoprofen concentrations were determined from the CSF, plasma and protein-free plasma samples. METHODS:Children (n = 21), aged 13-94 months, were given intravenous ketoprofen (1 mg/kg) prior to surgery under spinal anaesthesia. Single venous blood and CSF samples from each patient were collected simultaneously 7-67 minutes after the drug administration. Ketoprofen concentrations in the samples were determined using gas chromatography-mass spectrometry. RESULTS:Ketoprofen entered the CSF and was detectable in all samples. However, CSF delivery was limited; the ratio of ketoprofen concentration in CSF to plasma remained below 0.006 at all times. Ketoprofen was highly bound (> 98%) to plasma proteins. The free ketoprofen fraction was not in equilibrium with the CSF, and no clear peak drug concentration in the CSF was observed. CONCLUSION: This study shows that ketoprofen is able to enter the CSF of children, which enables central analgesic effects of ketoprofen. However, the slow distribution of ketoprofen into the CSF and the apparently low absolute concentrations has to be taken into account when central analgesic effects are desired.
Authors: Rupert P Austin; Patrick Barton; Scott L Cockroft; Mark C Wenlock; Robert J Riley Journal: Drug Metab Dispos Date: 2002-12 Impact factor: 3.922
Authors: Christopher Brasher; Benjamin Gafsous; Sophie Dugue; Anne Thiollier; Joelle Kinderf; Yves Nivoche; Robert Grace; Souhayl Dahmani Journal: Paediatr Drugs Date: 2014-04 Impact factor: 3.022
Authors: Adrianne G Huxtable; Stephanie M C Smith; Timothy J Peterson; Jyoti J Watters; Gordon S Mitchell Journal: J Neurosci Date: 2015-04-29 Impact factor: 6.167
Authors: Victoria C Ziesenitz; Tatjana Welzel; Madelé van Dyk; Patrick Saur; Matthias Gorenflo; Johannes N van den Anker Journal: Paediatr Drugs Date: 2022-09-02 Impact factor: 3.930