Upper gastrointestinal safety evaluation of parecoxib sodium, a new parenteral cyclooxygenase-2-specific inhibitor, compared with ketorolac, naproxen, and placebo.
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 i.v. parecoxib sodium (10 mg BID), oral naproxen (500 mg BID), or placebo for 7 days, or placebo for 2 days followed by i.v. 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.


CONCLUSIONS
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.
Harris
S I
SI
SeaView Research, Miami, Florida, USA.
Kuss
M
M
Hubbard
R C
RC
Goldstein
J L
JL
D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects* / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects*; D006801:Humans; D007263:Infusions, Parenteral; D007527:Isoenzymes; D007555:Isoxazoles / Q000009:adverse effects* / Q000627:therapeutic use*; D020910:Ketorolac / Q000009:adverse effects* / Q000627:therapeutic use*; D008297:Male; D008565:Membrane Proteins; D009288:Naproxen / Q000009:adverse effects* / Q000627:therapeutic use*; D010437:Peptic Ulcer / Q000139:chemically induced; D011451:Prostaglandin-Endoperoxide Synthases
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007555:Isoxazoles; D008565:Membrane Proteins; D009288:Naproxen; C409945:parecoxib; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D020910:Ketorolac