title: Cerebrospinal fluid distribution of ketoprofen after intravenous administration in young children.
abstract: 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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Pharmaceutical Chemistry, University of Kuopio, Kuopio, Finland. anne.mannila@uku.fi
authors.forename: Anne
authors.initials: A
authors.lastname: Mannila
authors.forename: Hannu
authors.initials: H
authors.lastname: Kokki
authors.forename: Marja
authors.initials: M
authors.lastname: Heikkinen
authors.forename: Merja
authors.initials: M
authors.lastname: Laisalmi
authors.forename: Marko
authors.initials: M
authors.lastname: Lehtonen
authors.forename: Hanna L
authors.initials: HL
authors.lastname: Louhisto
authors.forename: Tomi
authors.initials: T
authors.lastname: Järvinen
authors.forename: Jouko
authors.initials: J
authors.lastname: Savolainen
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid*; D001798:Blood Proteins / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D007660:Ketoprofen / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid*; D008297:Male; D011446:Prospective Studies; D011485:Protein Binding
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001798:Blood Proteins; D007660:Ketoprofen