Platelet function following administration of a novel formulation of intravenous diclofenac sodium versus active comparators: a randomized, single dose, crossover study in healthy male volunteers

Study Objective: To assess platelet function and safety following single-dose administration of a novel formulation of intravenous (IV) diclofenac sodium (Dyloject) 37.5 mg versus oral diclofenac 50 mg, IV ketorolac 30 mg, and oral acetylsalicylic acid (ASA) 325 mg. Design: Open-label, randomized, single-dose, 4-treatment crossover study. Setting: Clinical research unit. Patients: 30 healthy, ASA physical status I adult men. Interventions: Subjects were randomized to one of 6 treatment sequences that included 4 single-dose treatments. Study drug administration occurred on Days 1, 3, 5, and 7. Measurements: Platelet count, closure time as measured by platelet function analyzer (PFA-100), prothrombin time (PT), activated partial thromboplastin time (aPTT), and plasma concentrations of the study drugs were obtained over 24 hours after each treatment. The primary endpoint was the area under the curve for PFA collagen-epinephrine (CEPI) closure time difference from 0-6 hours post-drug administration (AUC(0-6h)). Secondary endpoints included the maximum change from baseline in PFA CEPI closure time. Main Results: AUC(0-6h) (mean +/- SD) for CEPI closure time difference was significantly smaller after IV diclofenac 37.5 mg (249 +/- 216 sec.hrs) than after ketorolac [and ASA (950 287 sec.hrs and 834 237 sec.hrs, respectively); P <= 0.0001 for both] but not after the oral diclofenac control (286 265 sec.hrs; P = 0.40). Similarly, the maximum change from baseline in PFA CEPI closure time was lower after IV diclofenac than after ketorolac or ASA across all time intervals examined. There were no significant changes in PT or aPTT at any time point with any treatment. There was a low frequency of adverse events. Conclusions: Acetylsalicylic acid and ketorolac both substantially disrupted platelet function in contrast to IV diclofenac 37.5 mg or oral diclofenac 50 mg control. Diclofenac, with its balanced COX-1 and COX-2 inhibitory profile, may pose less risk of postoperative bleeding than nonsteroidal anti inflammatory drugs (NSAIDs) such as ketorolac and ASA, which predominantly inhibit COX-1 (C) 2010 Elsevier Inc. All rights reserved.