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

Background. Acetaminophen (paracetamol) alone or in combinationwith other analgesics is widely used for postoperative analgesia.While acetaminophen and non-steroidal anti-inflammatory drugsinhibit platelet function, the cyclooxygenase-2 (COX-2) selectivelyinhibiting coxibs show no interference with platelet function.The authors studied the effect of a combination of i.v. parecoxiband acetaminophen on platelet function in healthy volunteers. Methods. Eighteen healthy, male volunteers (22–33 yr)received i.v. acetaminophen 1 g, parecoxib 40 mg+acetaminophen1 g or placebo in a double-blind, crossover study. Plateletfunction was assessed by photometric aggregometry and by measuringthe release of thromboxane B₂. Plasma acetaminophen concentrationswere 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 and4.2x10³ area units (P=0.02, all groups) after placebo, acetaminophenand parecoxib+acetaminophen, respectively. Inhibition of plateletaggregation showed no difference between acetaminophen aloneand the combination (P=0.82). Aggregation triggered with arachidonicacid 750 or 1000 µM, adenosine diphosphate (ADP) 1.5 or3 µM, or epinephrine 5 µM showed no differencesbetween the groups. Release of thromboxane B₂ in response toADP was inhibited similarly by both acetaminophen and the combination.Plasma acetaminophen concentrations were similar after acetaminophenand the combination. Conclusions. Acetaminophen and parecoxib showed no interactionin inhibiting platelet function. In combination they cause amild degree of COX-1 inhibition corresponding to that of acetaminophenalone.