Effects of parecoxib and dipyrone on platelet aggregation in patients undergoing meniscectomy: a double-blind, randomized, parallel-group study.
BACKGROUND
Based on a PubMed search of the literature using the terms parecoxib, platelets, thromboxane, bleeding, and platelet aggregation, the effects of parecoxib on platelet function have not fully been established under clinical conditions.


OBJECTIVE
The aim of this study was to determine platelet aggregation, thromboxane B(2) (TxB(2)) formation, and plasma concentrations with the use of parecoxib in postoperative pain management.


METHODS
This double-blind, randomized, parallel-group trial was conducted at the University Hospital for Orthopedic Surgery, Friedrichsheim, Frankfurt, Germany. Male and female patients aged 18 to 55 years and scheduled to undergo routine partial meniscectomy (or a similar arthroscopic procedure) were eligible. All patients received dose-adjusted enoxaparin before surgery and parecoxib 40 mg BID or dipyrone 1000 mg QID. Blood samples were drawn before first injection (predose) and at 0.5, 2, and 6 hours after injection. Platelet aggregation (expressed as percentage of the maximal light transmittance [A(max)]) was induced with arachidonic acid (A(max)AA) and collagen (A(max)CO). TxB(2) formation was determined using enzyme-linked immunosorbent assay.


RESULTS
This study included 26 patients. In both treatment groups, 8 males and 5 females, all white, were enrolled. In the dipyrone group, the mean age was 48 years (range, 32-61 years) and the mean weight was 85 kg (range, 63-122 kg); in the parecoxib group, the mean age was 47 years (range, 31-61 years) and the mean weight was 81 kg (range, 57-100 kg). Median (interquartile range [IQR]) predose values for A(max)AA were 76% (65%-83%) in the parecoxib group and 87% (80%-89%) in the dipyrone group. At 0.5 hour after injection, A(max)AA was 52% (5%-77%) with parecoxib and 8% (0%-11%) with dipyrone (P=0.004). At 2 hours after injection, A(max)AA was 78% (72%-80%) in the parecoxib group versus 7% (5%-11%) in the dipyrone group (P<0.001). At 6 hours after study drug administration, no treatment differences were found. For A(max)CO, no statistically significant differences were found. Consistent with the stronger inhibition of aggregation, patients who received dipyrone had lower TxB(2) formation values. Six hours after parecoxib administration, mean TxB(2) formation was significantly enhanced compared with predose values (132 ng/mL [IQR, 62-228 ng/mL] vs 185 ng/mL [IQR, 135-239 ng/mL]; P=0.05).


CONCLUSIONS
Platelet aggregation and TxB(2) formation were significantly lower for 6 hours in dipyronetreated patients compared with parecoxib-treated patients. In contrast, TxB(2) formation was increased with parecoxib 6 hours after administration compared with pretreatment values. In this small study, parecoxib did not affect platelet aggregation in a population of patients undergoing routine partial meniscectomy (or a similar arthroscopic procedure) under clinical conditions.
Graff
Jochen
J
Pharmazentrum Frankfurt/ZAFES(Center of Drug Research, Development, and Safety), Institute of Clinical Pharmacology, University Hospital Frankfurt am Main, Frankfurt, Germany. graff@em.uni-frankfurt.de
Arabmotlagh
Mohammed
M
Cheung
Raymond
R
Geisslinger
Gerd
G
Harder
Sebastian
S
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D001182:Arthroscopy; D002648:Child; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D004177:Dipyrone / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D017984:Enoxaparin / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010149:Postoperative Pain / Q000188:drug therapy; D010974:Platelet Aggregation / Q000187:drug effects*; D013929:Thromboxane B2 / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D017984:Enoxaparin; D007555:Isoxazoles; D013929:Thromboxane B2; D004177:Dipyrone; C409945:parecoxib