Diclofenac readily penetrates the cerebrospinal fluid in children.
BACKGROUND
Diclofenac, a nonselective nonsteroidal anti-inflammatory drug,, exerts analgesic action both in the peripheral tissues and in the central nervous system by inhibiting cyclooxygenase enzymes COX-1/2, but central nervous system penetration of diclofenac has not been evaluated in humans.


CONCLUSIONS
Diclofenac penetrates the cerebrospinal fluid rapidly, and after a single intravenous dose of 1 mg kg(-1), sufficient concentrations to inhibit COX-1/2 are sustained for up to 4 h.


OBJECTIVE
The primary aim was to study the cerebrospinal fluid (CSF) penetration of intravenous diclofenac in children. The secondary aim was to evaluate the plasma diclofenac concentration at the onset of wound pain after inguinal surgery in children.


METHODS
A total of 31 children (24 boys) aged 3 months to 12 years received a single intravenous injection of diclofenac 1 mg kg(-1). Paired CSF and blood samples were obtained 5 min to 22 h (median 69 min) later. In children having inguinal surgery a second blood sample was obtained at the time that the children felt wound pain for the first time after surgery. Diclofenac concentrations in CSF, plasma and protein free plasma were measured by gas chromatography with mass spectrometric detection.


RESULTS
In the 28 CSF samples obtained at 5 min to 3 h 43 min after injection, diclofenac concentrations ranged between 0.5 and 4.7 microg l(-1). At 5.5 h the CSF concentration was 0.1 microg l(-1), and no diclofenac was detected in the two CSF samples obtained at 22 h. The median of plasma diclofenac concentration at the time when pain returned after inguinal surgery was 104 microg l(-1) (range 70-272 microg l(-1)). No serious or unexpected adverse effects were reported.


CONCLUSIONS
Diclofenac penetrates the CSF rapidly, and a sufficient concentration to inhibit cyclooxygenase enzymes is sustained for up to 4 h.
Kokki
Hannu
H
Department of Pharmacology and Toxicology, University of Kuopio, Kuopio, Finland. hannu.kokki@kuh.fi
Kumpulainen
Elina
E
Laisalmi
Merja
M
Savolainen
Jouko
J
Rautio
Jarkko
J
Lehtonen
Marko
M
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid*; D002555:Cerebrospinal Fluid / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid*; D004008:Diclofenac / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D007223:Infant; D007275:Injections, Intravenous; D008297:Male; D010149:Postoperative Pain / Q000517:prevention & control*; D013223:Statistics as Topic; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D004008:Diclofenac