J Clin Pharmacol
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First published on February 13, 2008, doi:10.1177/0091270007313389

The Journal of Clinical Pharmacology 2008;48:495.

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©© 2008 American College of Clinical Pharmacology, Inc.
The Journal of Clinical Pharmacology , 10.1177/0091270007313389


Article

How Readily Does Ketorolac Penetrate Cerebrospinal Fluid in Children?

Elina Kumpulainen 1, Hannu Kokki 1*, Merja Laisalmi 2, Marja Heikkinen 2, Jouko Savolainen 3, Jarkko Rautio 4, and Marko Lehtonen 4

1 University of Kuopio and Kuopio University Hospital
2 Kuopio University Hospital
3 Fennopharma Ltd
4 University of Kuopio

* To whom correspondence should be addressed. E-mail: hannu.kokki{at}kuh.fi.


   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·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 µg·L–1 (median, 0.6 µg·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.
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