Propacetamol augments inhibition of platelet function by diclofenac in volunteers

Br J Anaesth. 2003 Sep;91(3):357-62. doi: 10.1093/bja/aeg195.

Abstract

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / analogs & derivatives*
  • Acetaminophen / pharmacology*
  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Blood Platelets / drug effects*
  • Cross-Over Studies
  • Cyclooxygenase 1
  • Cyclooxygenase Inhibitors / pharmacology*
  • Diclofenac / pharmacology*
  • Double-Blind Method
  • Drug Synergism
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Male
  • Membrane Proteins
  • Pain Measurement
  • Platelet Aggregation / drug effects*
  • Platelet Function Tests / methods
  • Prostaglandin-Endoperoxide Synthases

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • Diclofenac
  • Acetaminophen
  • propacetamol
  • Cyclooxygenase 1
  • PTGS1 protein, human
  • Prostaglandin-Endoperoxide Synthases