title: How readily does ketorolac penetrate cerebrospinal fluid in children?
abstract: Ketorolac is a potent nonsteroidal anti-inflammatory analgesic used in postoperative pain management. Ketorolac elicits its analgesic action by inhibiting the cyclo-oxygenase enzyme in peripheral tissues and in the spinal cord. Central nervous system penetration of parenteral ketorolac has been evaluated in adults but not in children. In the present study we investigated ketorolac cerebrospinal fluid penetration via spinal anesthesia in 30 healthy children undergoing surgery in the lower part of the body. A single cerebrospinal fluid and blood sample was obtained between 11 minutes and 6 hours after receiving ketorolac 0.5 mg x kg(-1) IV. Ketorolac concentrations were determined by gas chromatography with mass spectrometric detection. Ketorolac was detected from 22 of the 30 cerebrospinal fluid samples, and the concentrations ranged between 0.2 and 7.6 microg x L(-1) (median, 0.6 microg x L(-1)). The cerebrospinal fluid to unbound plasma concentration-ratio ranged between 0.01 and 0.69 (median, 0.08). These low concentrations indicate that ketorolac does not readily penetrate cerebrospinal fluid in children.
authors.affiliation: Department of Pharmacology and Toxicology, University of Kuopio, Kuopio, Finland.
authors.forename: Elina
authors.initials: E
authors.lastname: Kumpulainen
authors.forename: Hannu
authors.initials: H
authors.lastname: Kokki
authors.forename: Merja
authors.initials: M
authors.lastname: Laisalmi
authors.forename: Marja
authors.initials: M
authors.lastname: Heikkinen
authors.forename: Jouko
authors.initials: J
authors.lastname: Savolainen
authors.forename: Jarkko
authors.initials: J
authors.lastname: Rautio
authors.forename: Marko
authors.initials: M
authors.lastname: Lehtonen
mesh_terms: D000293:Adolescent; D000775:Anesthesia, Spinal; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics; D001812:Blood-Brain Barrier; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007275:Injections, Intravenous; D020910:Ketorolac / Q000097:blood / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics; D008297:Male; D011446:Prospective Studies; D018401:Sample Size; D013514:Surgical Procedures, Operative
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D020910:Ketorolac