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

Abstract

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. 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 B(2). Plasma acetaminophen concentrations were measured by high-performance liquid chromatography. Platelet aggregation (median area under the curve) triggered with arachidonic acid 500 microM was 24.6, 3.9 and 4.2x10(3) 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 microM, adenosine diphosphate (ADP) 1.5 or 3 microM, or epinephrine 5 microM showed no differences between the groups. Release of thromboxane B(2) in response to ADP was inhibited similarly by both acetaminophen and the combination. Plasma acetaminophen concentrations were similar after acetaminophen and the combination. 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.