Published online October 1, 2007
PEDIATRICS Vol. 120 No. 4 October 2007, pp. e1002-e1008 (doi:10.1542/peds.2007-0064)
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ARTICLE

Cerebrospinal Fluid Distribution of Ibuprofen After Intravenous Administration in Children

Hannu Kokki, MD, PhDa,b, Elina Kumpulainen, BMa,b, Marko Lehtonen, MScc, Merja Laisalmi, MDb, Marja Heikkinen, MDd, Jouko Savolainen, PhDe and Jarkko Rautio, PhDc

a Departments of Pharmacology and Toxicology
c Pharmaceutical Chemistry, University of Kuopio, Kuopio, Finland
b Departments of Anesthesiology and Intensive Care
d Surgery, Kuopio University Hospital, Kuopio, Finland
e Oy Fennopharma Ltd, Kuopio, Finland

BACKGROUND. Ibuprofen is the most commonly used nonsteroidal, antipyretic, antiinflammatory analgesic in children. Nonsteroidal, antipyretic, antiinflammatory analgesics act in both the peripheral tissues and the central nervous system. The central nervous system penetration of ibuprofen has been described in adults but not in children.

OBJECTIVES. Our goals were to investigate the cerebrospinal fluid penetration of ibuprofen in children and evaluate the analgesic plasma concentration of ibuprofen after inguinal surgery in children.

MATERIALS AND METHODS. A total 36 healthy children (25 boys) aged 3 months to 12 years received a single intravenous injection of ibuprofen (10 mg/kg). A paired cerebrospinal fluid and blood sample was obtained 10 minutes to 8 hours after the injection. In children having inguinal surgery, a second blood sample was obtained at the time that the child first had wound pain.

RESULTS. The ibuprofen level was determined in all cerebrospinal fluid and plasma samples. Cerebrospinal fluid concentrations ranged between 15 and 541 µg/L, and the highest concentrations were measured 30 to 38 minutes after dosing. In all cerebrospinal fluid samples collected after 30 minutes, ibuprofen concentration exceeded that of unbound plasma. The plasma analgesic concentrations after inguinal surgery ranged between 10 and 25 mg/L.

CONCLUSIONS. Ibuprofen penetrates the cerebrospinal fluid readily, with peak concentrations attained 30 to 40 minutes after intravenous injection of a 10 mg/kg dose. The plasma analgesic concentration after inguinal surgery with spinal anesthesia is 10 to 25 mg/L.

Key Words: ibuprofen • cerebrospinal fluid • pharmacology • pharmacokinetics • analgesic concentration • child • infant

Abbreviations: NSAID—nonsteroidal antiinflammatory drug • CNS—central nervous system • PGE2— prostaglandin E2 • CSF—cerebrospinal fluid • PACU—postanesthesia care unit • BCSFB—blood-cerebrospinal fluid barrier

Accepted Mar 14, 2007.




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E. Kumpulainen, H. Kokki, M. Laisalmi, M. Heikkinen, J. Savolainen, J. Rautio, and M. Lehtonen
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