thromboxane-b2 and parecoxib

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.. 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.. 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.. 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).. 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.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthroscopy; Child; Cyclooxygenase Inhibitors; Dipyrone; Double-Blind Method; Drug Therapy, Combination; Enoxaparin; Enzyme-Linked Immunosorbent Assay; Female; Humans; Isoxazoles; Male; Middle Aged; Pain, Postoperative; Platelet Aggregation; Thromboxane B2

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.

Topics: Acetaminophen; Adenosine Diphosphate; Adult; Analgesics, Non-Narcotic; Arachidonic Acid; Blood Platelets; Cross-Over Studies; Cyclooxygenase Inhibitors; Double-Blind Method; Drug Administration Schedule; Drug Interactions; Epinephrine; Humans; Infusions, Intravenous; Isoxazoles; Male; Platelet Aggregation; Thromboxane B2