Influence on platelet aggregation of i.v. parecoxib and acetaminophen in healthy volunteers.
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 B(2). Plasma acetaminophen concentrations were measured by high-performance liquid chromatography.


RESULTS
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.


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.
Munsterhjelm
E
E
Department of Anaesthesiology and Intensive Care Medicine, Helsinki University Hospital, Helsinki, Finland. edward.munsterhjelm@hus.fi
Niemi
T T
TT
Ylikorkala
O
O
Neuvonen
P J
PJ
Rosenberg
P H
PH
D000082:Acetaminophen / Q000008:administration & dosage* / Q000097:blood; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000097:blood; D016718:Arachidonic Acid / Q000032:analysis / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D007262:Infusions, Intravenous; D007555:Isoxazoles / Q000008:administration & dosage*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D013929:Thromboxane B2 / Q000097:blood
D018712:Analgesics, Non-Narcotic; D016861:Cyclooxygenase Inhibitors; D007555:Isoxazoles; D016718:Arachidonic Acid; D000082:Acetaminophen; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; C409945:parecoxib; D004837:Epinephrine