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BJA Advance Access published online on May 12, 2006
British Journal of Anaesthesia, doi:10.1093/bja/ael108
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© The Board of Management and Trustees of the British Journal of Anaesthesia 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Accepted March 29, 2006

Clinical Investigation

Influence on platelet aggregation of i.v. parecoxib and acetaminophen in healthy volunteers

E. Munsterhjelm 1 *, T. T. Niemi 1, O. Ylikorkala 2, P. J. Neuvonen 3, and P. H. Rosenberg 1

1 Department of Anaesthesiology and Intensive Care Medicine, Helsinki University Hospital, Helsinki, Finland
2 Department of Obstetrics and Gynaecology, Helsinki University Hospital, Helsinki, Finland
3 Department of Clinical Pharmacology, Helsinki University Hospital, Helsinki, Finland

* To whom correspondence should be addressed.
E. Munsterhjelm, E-mail: edward.munsterhjelm{at}hus.fi


  Abstract

Background. Acetaminophen (paracetamol) alone or in combination with other analgesics is widely used for postoperative analgesia. While acetaminophen and non-steroidal anti-inflammatory drugs inhibit platelet function, the cyclooxygenase-2 (COX-2) selectively inhibiting coxibs show no interference with platelet function. The authors studied the effect of a combination of i.v. parecoxib and acetaminophen on platelet function in healthy volunteers.

Methods. Eighteen healthy, male volunteers (22-33 yr) received i.v. acetaminophen 1 g, parecoxib 40 mg+acetaminophen 1 g or placebo in a double-blind, crossover study. Platelet function was assessed by photometric aggregometry and by measuring the release of thromboxane B2. Plasma acetaminophen concentrations were measured by high-performance liquid chromatography.

Results. Platelet aggregation (median area under the curve) triggered with arachidonic acid 500 µM was 24.6, 3.9 and 4.2x103 area units (P=0.02, all groups) after placebo, acetaminophen and parecoxib+acetaminophen, respectively. Inhibition of platelet aggregation showed no difference between acetaminophen alone and the combination (P=0.82). Aggregation triggered with arachidonic acid 750 or 1000 µM, adenosine diphosphate (ADP) 1.5 or 3 µM, or epinephrine 5 µM showed no differences between the groups. Release of thromboxane B2 in response to ADP was inhibited similarly by both acetaminophen and the combination. Plasma acetaminophen concentrations were similar after acetaminophen and the combination.

Conclusions. Acetaminophen and parecoxib showed no interaction in inhibiting platelet function. In combination they cause a mild degree of COX-1 inhibition corresponding to that of acetaminophen alone.

Keywords: analgesics non-opioid, acetaminophen; blood, platelets; pharmacology, drug interactions; thromboxane.
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