HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Sign In to gain access to subscriptions and/or personal tools.

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (31) Citing Articles via Google Scholar Google Scholar Articles by Dallob, A. Articles by Gottesdiener, K. Search for Related Content PubMed PubMed Citation Articles by Dallob, A. Articles by Gottesdiener, K. Social Bookmarking                   What's this?

Characterization of Etoricoxib, a Novel, Selective COX-2 Inhibitor

From the Clinical Development Laboratory (Ms. Dallob), Clinical Biostatistics (Ms. Wong), Clinical Research (Dr. DeTora), and Clinical Pharmacology (Dr. Gertz, Dr. Wagner, Dr. Gottesdiener), Merck Research Laboratories, Rahway, New Jersey; Division of Gastroenterology, University Hospital, Nottingham, United Kingdom (Dr. Hawkey, Mr. Wight); Division of Clinical Pharmacology, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania (Dr. Greenberg, Dr. Waldman); Department of Clinical Pharmacology, University Hospital, Leuven, Belgium (Dr. De Schepper); and Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania (Dr. Agrawal).

Etoricoxib is a potent selective COX-2 inhibitor in man. Ex vivo whole-blood assays assessed COX-2 inhibition after oral administration of etoricoxib in single (5-500 mg) and multiple (25-150 mg) once-daily doses to healthy human subjects. A separate study examined ex vivo gastric mucosal PGE₂ synthesis after etoricoxib (120 mg qd), naproxen (500 mg bid), or placebo for 5 days. The effect of etoricoxib 120 mg qd on the COX-1-mediated antiplatelet effects of low-dose aspirin (ASA) was also assessed. The mean (time)-weighted average inhibition (WAI) of lipopolysaccharide (LPS)-stimulated PGE₂ (COX-2 assay) versus placebo was dose related after single (range: 3.1%-99.1%) and multiple doses (range: 52.5%-96.7%). PGE₂ remained significantly inhibited 24 hours postdose at steady state. Inhibition of LPS-stimulated PGE₂ showed a strong relationship with etoricoxib plasma concentrations; ex vivo, IC₅₀ was almost identical to in vitro. Multiple dosing of etoricoxib (up to 150 mg qd) showed no important effects on serum TXB₂, bleeding time, or platelet aggregation (COX-1-mediated effects). The nonselective nonsteroidal anti-inflammatory (NSAID) naproxen significantly inhibited (78%) ex vivo prostaglandin synthesis in gastric mucosa; etoricoxib had no effect. Etoricoxib did not interfere with the antiplatelet effects of low-dose ASA, as assessed by serum TXB₂ and platelet aggregation. Etoricoxib was generally well tolerated, even at doses above the clinical dose range. Based on these results, etoricoxib is a potent selective inhibitor of COX-2 after single and multiple dosing regimens and does not inhibit prostaglandin synthesis in the gastric mucosa, even at doses above the clinical dose range of 60 to 120 mg.

Key Words: Etoricoxib • COX-2 inhibitor • NSAIDs • whole-blood assays • gastric biopsy study • pharmacokinetics • pharmacodynamics • aspirin

Address for reprints: Aimee Dallob, RY50-100, Box 2000, Rahway, NJ 07065.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. Chilet-Rosell, M.T. Ruiz-Cantero, and J.F. Horga Women's health and gender-based clinical trials on etoricoxib: methodological gender bias J. Public Health Med., March 14, 2009; (2009) fdp024v1. [Abstract] [Full Text] [PDF]

				J. I. Schwartz, A. L. Dallob, P. J. Larson, O. F. Laterza, J. Miller, J. Royalty, K. M. Snyder, D. L. Chappell, D. A. Hilliard, M. E. Flynn, et al. Comparative Inhibitory Activity of Etoricoxib, Celecoxib, and Diclofenac on COX-2 Versus COX-1 in Healthy Subjects J. Clin. Pharmacol., June 1, 2008; 48(6): 745 - 754. [Abstract] [Full Text] [PDF]

				J. I. Schwartz, C. Thach, K. C. Lasseter, J. Miller, D. Hreniuk, D. A. Hilliard, K. M. Snyder, B. J. Gertz, and K. M. Gottesdiener Effects of Etoricoxib and Comparator Nonsteroidal Anti-Inflammatory Drugs on Urinary Sodium Excretion, Blood Pressure, and Other Renal Function Indicators in Elderly Subjects Consuming a Controlled Sodium Diet J. Clin. Pharmacol., December 1, 2007; 47(12): 1521 - 1531. [Abstract] [Full Text] [PDF]

				J. I. Schwartz, N. G. B. Agrawal, A. H. Hartford, J. Cote, T. L. Hunt, R. Verbesselt, D. R. Eckols, and K. M. Gottesdiener The Effect of Etoricoxib on the Pharmacodynamics and Pharmacokinetics of Warfarin J. Clin. Pharmacol., May 1, 2007; 47(5): 620 - 627. [Abstract] [Full Text] [PDF]

				C. Tsoukas, M. E. Eyster, S. Shingo, S. Mukhopadhyay, K. M. Giallella, S. P. Curtis, A. S. Reicin, and A. Melian Evaluation of the efficacy and safety of etoricoxib in the treatment of hemophilic arthropathy Blood, March 1, 2006; 107(5): 1785 - 1790. [Abstract] [Full Text] [PDF]

				G. L. Rasmussen, K. Malmstrom, M. H. Bourne, M. Jove, S. M. Rhondeau, P. Kotey, J. Ang, M. Aversano, A. S. Reicin, and for the Etoricoxib Postorthopedic Study Group Etoricoxib Provides Analgesic Efficacy to Patients After Knee or Hip Replacement Surgery: A Randomized, Double-Blind, Placebo-Controlled Study Anesth. Analg., October 1, 2005; 101(4): 1104 - 1111. [Abstract] [Full Text] [PDF]

				N. G. B. Agrawal, C. Z. Matthews, R. S. Mazenko, E. J. Woolf, A. G. Porras, X. Chen, J. L. Miller, N. Michiels, M. Wehling, A. Schultz, et al. The Effects of Modifying In Vivo Cytochrome P450 3A (CYP3A) Activity on Etoricoxib Pharmacokinetics and of Etoricoxib Administration on CYP3A Activity J. Clin. Pharmacol., October 1, 2004; 44(10): 1125 - 1131. [Abstract] [Full Text] [PDF]

				D. J. Chang, P. J. Desjardins, T. R. King, T. Erb, and G. P. Geba The Analgesic Efficacy of Etoricoxib Compared with Oxycodone/Acetaminophen in an Acute Postoperative Pain Model: A Randomized, Double-Blind Clinical Trial Anesth. Analg., September 1, 2004; 99(3): 807 - 815. [Abstract] [Full Text] [PDF]