Cerebrospinal Fluid Distribution of Ketoprofen after Intravenous Administration in Young Children
- PDF / 128,630 Bytes
- 7 Pages / 504.57 x 720 pts Page_size
- 60 Downloads / 147 Views
Clin Pharmacokinet 2006; 45 (7): 737-743 0312-5963/06/0007-0737/$39.95/0 © 2006 Adis Data Information BV. All rights reserved.
Cerebrospinal Fluid Distribution of Ketoprofen after Intravenous Administration in Young Children Anne Mannila,1 Hannu Kokki,2,3 Marja Heikkinen,4 Merja Laisalmi,2 Marko Lehtonen,1 Hanna L. Louhisto,3 Tomi J¨arvinen1 and Jouko Savolainen1 1 2 3 4
Department of Pharmaceutical Chemistry, University of Kuopio, Kuopio, Finland Department of Anaesthesiology and Intensive Care, Kuopio University Hospital, Kuopio, Finland Department of Pharmacology and Toxicology, University of Kuopio, Kuopio, Finland Department of Surgery, Kuopio University Hospital, Kuopio, Finland
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. 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.
Background Ketoprofen (2-(3-benzoylphenyl)propionic acid) is a traditional NSAID. It has analgesic, anti-inflammatory and antipyretic properties, which are thought to result mainly from peripheral inhibition of the cyclooxygenase (COX) enzyme. However, it has been suggested that, in addition to peripheral sites of action, ketoprofen has central effects.[1,2] The central effects may be mediated by inhibition of COX, but it has been suggested that other mechanisms may be involved.
In order to have central effects a drug has to pass the blood-brain barrier and/or the blood-cerebrospinal fluid (CSF) barrier, which separate circulating blood from the brain and the CSF, respectively. These barriers efficiently control the exchange of substances between blood and the CNS. In principle, a drug molecule has to be either small and lipophilic enough, or a substrate to a transport protein located at the blood-brain/CSF barrier to be able to pass into the CNS. Ketoprofen has a small molecular weight (254 g/mol) and is highly lipophilic in its unionised form; its logarit
Data Loading...
