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 - 07/08/11
: Chief Medical OfficerAbstract |
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 (AUC0-6h). Secondary endpoints included the maximum change from baseline in PFA CEPI closure time.
Main Results |
AUC0-6h (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 antiinflammatory drugs (NSAIDs) such as ketorolac and ASA, which predominantly inhibit COX-1.
Le texte complet de cet article est disponible en PDF.Keywords : Diclofenac, Nonsteroidal anti-inflammatory drugs, Postoperative, Platelets, Multimodal, COX-1/COX-2
Plan
| ☆ | Conflict of Interest: Funding for this study was exclusively provided by Javelin Pharmaceuticals, Inc. (Javelin). Four authors – Daniel Carr, Ryan Lanier, Jianyuan Wang, and Curtis Wright – are or were employed by Javelin during this study. As Javelin employees, these four authors had financial interest in the subject matter, materials, equipment, or devices discussed in this manuscript. However, the investigators who conducted the study had no financial interests in Javelin beyond reimbursement of the costs of the investigation. |
Vol 22 - N° 7
P. 510-518 - novembre 2010 Retour au numéro
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