Cerebrospinal fluid and plasma concentrations of dipyrone metabolites after a single oral dose of dipyrone.
OBJECTIVE
Dipyrone is a veteran analgesic and antipyretic drug. After oral administration it is rapidly converted by hydrolysis to 4-methylaminoantipyrine (MAA), which is further metabolized to 4-formylaminoantipyrine (FAA), 4-aminoantipyrine (AA) and 4-acetylaminoantipyrine (AAA). It is still debated whether the site of dipyrone action is in the central nervous system or in the periphery. The purpose of this study was to assess whether dipyrone metabolites cross the blood-brain barrier (BBB) when administered systemically.


METHODS
Twenty-eight patients undergoing diagnostic lumbar puncture (LP) were randomly assigned to receive two 0.5-g dipyrone tablets either 30 min, 1, 1.5, 2, 4, 6, 8 h or 12 h before the lumbar tap. A 5-ml blood sample was drawn concomitantly.


RESULTS
All four metabolites were found in the cerebrospinal fluid (CSF). Their appearance in the CSF lagged but followed that found in the plasma. Mean CSF/plasma ratios were 0.40 (for samples taken between 0.5-2 h) and 0.83 (for samples taken between 4-12 h) for MAA, 0.62 for AA, 0.55 for FAA and 0.40 for AAA (for all samples). Significant correlation was found between plasma and CSF concentrations for MAA, AA, FAA and AAA.


CONCLUSIONS
The concentration-time course of dipyrone metabolite CSF concentrations are in agreement with that of their plasma concentrations and the analgesic effect of dipyrone.
Cohen
O
O
Department of Medicine, Hadassah University Hospital, Jerusalem, Israel.
Zylber-Katz
E
E
Caraco
Y
Y
Granit
L
L
Levy
M
M
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000632:Aminopyrine / Q000031:analogs & derivatives / Q000097:blood / Q000134:cerebrospinal fluid; D000675:Ampyrone / Q000031:analogs & derivatives / Q000097:blood / Q000134:cerebrospinal fluid; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics; D001812:Blood-Brain Barrier; D004177:Dipyrone / Q000031:analogs & derivatives / Q000097:blood / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D047069:Pyrazolones; D013129:Spinal Puncture / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D047069:Pyrazolones; D000632:Aminopyrine; D000675:Ampyrone; C011256:4-formylaminoantipyrine; D004177:Dipyrone; C010403:N-acetylaminoantipyrine; C008667:noramidopyrine