J Clin Pharmacol
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PEDIATRICS

How Readily Does Ketorolac Penetrate Cerebrospinal Fluid in Children?

Elina Kumpulainen, BM, Hannu Kokki, MD, PhD, Merja Laisalmi, MD, PhD, Marja Heikkinen, MD, Jouko Savolainen, PhD, Jarkko Rautio, PhD and Marko Lehtonen, MSc

From the Department of Pharmacology and Toxicology, University of Kuopio (Ms Kumpulainen, Dr Kokki); the Department of Anesthesiology and Intensive Care, Kuopio University Hospital (Ms Kumpulainen, Dr Kokki, Dr Laisalmi); the Department of Surgery, Kuopio University Hospital (Dr Heikkinen); Oy Fennopharma Ltd (Dr Savolainen); and the Department of Pharmaceutical Chemistry (Dr Rautio, Mr Lehtonen), University of Kuopio, Kuopio, Finland.

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.

Key Words: Ketorolac • cerebrospinal fluid • pharmacokinetics • child • infant

Address for correspondence: Hannu Kokki, MD, PhD, Department of Anesthesiology and Intensive Care, PO Box 1777, FI-70211 Kuopio, Finland; e-mail: hannu.kokki{at}kuh.fi.






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