Propacetamol augments inhibition of platelet function by diclofenac in volunteers.
BACKGROUND
Acetaminophen (paracetamol) enhances the analgesic effect of non-steroidal anti-inflammatory drugs (NSAIDs). Acetaminophen is a weak inhibitor of cyclooxygenase (COX), and its combination with an NSAID may augment COX inhibition-related side effects.


METHODS
Ten healthy male volunteers (21-30 yr) were given diclofenac 1.1 mg kg(-1) alone, a combination of propacetamol 30 mg kg(-1) (which is hydrolysed to 50% acetaminophen) and diclofenac 1.1 mg kg(-1) or placebo intravenously in a double blind, crossover study. Platelet function was assessed at 5 min, 90 min and 22-24 h by photometric aggregometry, platelet function analyser (PFA-100(TM)) and by measuring the release of thromboxane B(2) (TxB(2)). Analgesia was assessed with the cold pressor test.


RESULTS
Platelet aggregation induced with arachidonic acid was fully inhibited by both diclofenac alone and the combination at the end of the 30-min drug infusion. Propacetamol augmented the inhibition by diclofenac at 90 min (P=0.014). At 22-24 h, platelet function had fully recovered. TxB(2) release was inhibited by the combination of propacetamol and diclofenac at 90 min in comparison with diclofenac alone (P=0.027). PFA-100(TM) detected no difference in platelet function between these two groups. No analgesic effect was detected with the cold pressor test.


CONCLUSIONS
The combination of propacetamol and diclofenac inhibits platelet function more than diclofenac alone. This should be considered when assessing the risk of surgical bleeding.
Munsterhjelm
E
E
Department of Anaesthesiology and Intensive Care Medicine, Helsinki University Hospital, PO Box 340 (P-floor), FIN-00029 HUS, Helsinki, Finland. edward.munsterhjelm@hus.fi
Niemi
T T
TT
Syrjälä
M T
MT
Ylikorkala
O
O
Rosenberg
P H
PH
D000082:Acetaminophen / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D018592:Cross-Over Studies; D051545:Cyclooxygenase 1; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology*; D004311:Double-Blind Method; D004357:Drug Synergism; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008297:Male; D008565:Membrane Proteins; D010147:Pain Measurement; D010974:Platelet Aggregation / Q000187:drug effects*; D010979:Platelet Function Tests / Q000379:methods; D011451:Prostaglandin-Endoperoxide Synthases
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D004008:Diclofenac; D000082:Acetaminophen; C063776:propacetamol; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D011451:Prostaglandin-Endoperoxide Synthases