Cerebrospinal fluid distribution of ibuprofen after intravenous administration in children.
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.


OBJECTIVE
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.


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 microg/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.
Kokki
Hannu
H
Department of Pharmacology and Toxicology, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland. hannu.kokki@kuh.fi
Kumpulainen
Elina
E
Lehtonen
Marko
M
Laisalmi
Merja
M
Heikkinen
Marja
M
Savolainen
Jouko
J
Rautio
Jarkko
J
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid*; D007223:Infant; D007264:Inguinal Canal / Q000601:surgery; D007275:Injections, Intravenous; D008297:Male; D010149:Postoperative Pain / Q000517:prevention & control; D011446:Prospective Studies; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007052:Ibuprofen