Upper gastrointestinal safety evaluation of parecoxib sodium, a new parenteral cyclooxygenase-2—specific inhibitor, compared with ketorolac, naproxen, and placebo

• Published in: Clinical therapeutics 2001-09, Vol.23 (9), p.1422-1428
• Main Authors: Harris, Stuart I, Kuss, Michael, Hubbard, Richard C, Goldstein, Jay L
• Format: Article
• Language: English
• Subjects: Aged; Analgesics, Non-Narcotic - adverse effects; Analgesics, Non-Narcotic - therapeutic use; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Biological and medical sciences; COX-2 inhibitor; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - adverse effects; Cyclooxygenase Inhibitors - therapeutic use; Double-Blind Method; Drug toxicity and drugs side effects treatment; Female; Gastric Mucosa - drug effects; gastrointestinal toxicity; Humans; Infusions, Parenteral; Isoenzymes; Isoxazoles - adverse effects; Isoxazoles - therapeutic use; ketorolac; Ketorolac - adverse effects; Ketorolac - therapeutic use; Male; Medical sciences; Membrane Proteins; naproxen; Naproxen - adverse effects; Naproxen - therapeutic use; nonsteroidal anti-inflammatory drugs; parecoxib sodium; Peptic Ulcer - chemically induced; Pharmacology. Drug treatments; Prostaglandin-Endoperoxide Synthases; Toxicity: digestive system
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/S0149-2918(01)80117-X

Background: Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of ulcers and upper gastrointestinal (GI) ulcer complications, which has been attributed to the inhibition of cyclooxygenase-1. These risks are usually increased in elderly populations. Parecoxib sodium is an injectable prodrug of the cyclooxygenase-2—specific inhibitor valdecoxib that has exhibited analgesic activity in previous trials. Objective: The purpose of this study was to compare the GI safety and tolerability profile of parecoxib sodium with that of ketorolac, naproxen, and placebo in a 7-day endoscopic trial in elderly subjects. Methods: This was a randomized, double-blind, double-dummy, placebo-controlled, parallel-group study. After a normal baseline endoscopy, healthy elderly subjects aged 66 to 75 years were randomized to receive IV parecoxib sodium (10 mg BID), oral naproxen (500 mg BID), or placebo for 7 days, or placebo for 2 days followed by IV ketorolac (15 mg QID) for 5 days. Endoscopy was performed again after 7 days. Results: Among the first 17 subjects enrolled, ulcers were observed in all treatment groups except the parecoxib sodium group (ketorolac, 4 4 subjects; naproxen, 2 4 subjects; and placebo, 2 5 subjects). Four subjects in the ketorolac group and 1 subject in the naproxen group had multiple gastric ulcers or combined gastric and duodenal ulcers. Because of the unexpectedly high incidence of gastroduodenal ulcers observed, the study was terminated early and the randomization blind broken. Conclusion: These findings suggest that elderly patients may be at risk for GI ulceration even after short-term use of the conventional NSAIDs ketorolac and naproxen.