Etodolac, A Preferential COX-2 Inhibitor, Does Not Inhibit Platelet Aggregation in A Randomized Placebo-controlled Trial - Etodolac, A Preferential COX-2 Inhibitor, Does Not Inhibit Platelet Aggregation in A Randomized Placebo-controlled Trial - Open Access Pub

To date, platelet aggregation studies have not been formally evaluated in persons receiving Etodolac, a preferential cyclooxygenase-2 (COX-2) inhibitor. Our purpose was to investigate the influence of Etodolac in therapeutic (analgesic) doses (300 mg every 12h) on platelet aggregation as compared to placebo in healthy volunteers. Platelet aggregation, the primary efficacy variable in this trial, was performed according to the Born method with platelet rich plasma; it was evaluated as maximal platelet aggregation induced by 3 substances (adenosine diphosphate (ADP), epinephrine, collagen); each of these substances was used at 3 different concentrations. No significant difference in platelet aggregation as assessed by Born aggregometry was seen in volunteers treated with etodolac or placebo. Etodolac - applied in regular analgesic doses to volunteers - does not show an inhibitory effect on platelet aggregation and therefore seems an attractive analgesic substance for the perioperative setting. DOI10.14302/issn.2328-0182.japst-12-99 Research into cyclooxygenase inhibition lead to the identification of a constitutional cyclooxygenase activity (cyclooxygenase 1, COX-1), which can be distinguished from a cytokine-induced cyclooxygenase activity (cyclooxygenase 2, COX-2) 1. With the use of cyclooxygenase inhibitors as anti-inflammatory agents and analgesics, unwanted side effects such as mucosal toxicity can occur. It was postulated that such side effects are mainly associated to the effects of COX-1 inhibition 2; and that preferential inhibition of COX-2 would therefore decrease this type of toxicity 3. This lead to the development of preferential COX-2 inhibitors with effective anti-inflammatory and analgesic effects documented 4, 5. As postulated, it became apparent that COX-2 inhibition was indeed associated with a lower degree of mucosal toxicity 6. It was also shown that COX-2 activity is not involved in platelet thromboxane biosynthesis 7 and that selective COX-2 inhibition thus does not effect platelet thromboxane A2 (TxA2) dependent platelet aggregation 8. No such studies were published on the use of Etodolac (Lodine？, Sigma-Tau Pharma AG, Zofingen, Switzerland) in humans so far. Analgesic drugs that modify enzymatic pathways can influence platelet aggregability and use of non-steroidal anti-inflammatory drugs (NSAIDs) may lead to increased perioperative bleeding risk 9, 10, a side effect seen with COX inhibitors 11. Perioperative bleeding is becoming a more important issue for various reasons, including the increased frequency of regional anesthesia.