An endoscopic comparison of gastroduodenal injury with over-the-counter doses of ketoprofen and acetaminophen.
OBJECTIVE
The objective of this study was to endoscopically assess in healthy subjects the gastrointestinal effects of over-the-counter (OTC) doses of ketoprofen. Ketoprofen is a potent nonsteroidal antiinflammatory agent (NSAID) recently approved for OTC use as an analgesic/antipyretic at doses of 75 mg versus the usual dose of < or = 300 mg daily. In epidemiological studies, ketoprofen at prescription doses has consistently been in the higher relative risk group of NSAIDs in the occurrence of gastrointestinal complications of therapy. The gastrointestinal effects of the OTC (US) dose of ketoprofen have not been reported.


METHODS
In a randomized, double blind, three way crossover study, 24 healthy subjects received 7 days of therapy with ketoprofen 75 mg/day, acetaminophen 4000 mg/day, and placebo. Gastroduodenal endoscopy was performed before and at the end of each treatment period. The condition of the mucosa was graded compositely for the gastric antrum, fundus, body, and duodenum.


RESULTS
Significantly more frequent and severe gastric mucosal injury was observed after dosing with ketoprofen compared with acetaminophen (p = 0.0001). The acetaminophen group showed no difference from placebo (p = 0.8783). Two subjects developed frank gastric ulcers with ketoprofen therapy. Marginally more frequent (p = 0.0703) and significantly more severe (p = 0.0117) duodenal mucosal injury was seen. No significant differences were observed between treatment groups with respect to subjective symptoms of gastric discomfort or adverse events.


CONCLUSIONS
These results indicate that even at lower (OTC) doses (75 mg/day) ketoprofen is associated with significant gastrointestinal irritation.
Houston Institute of Clinical Research, Texas 77074, USA.
F L
FL
Lanza
J R
JR
Codispoti
E B
EB
Nelson
D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects*; D000293:Adolescent; D000328:Adult; D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000009:adverse effects*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004384:Duodenoscopy; D004386:Duodenum / Q000187:drug effects*; D005260:Female; D005748:Gastric Fundus / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects; D005773:Gastroscopy; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects; D007660:Ketoprofen / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D004366:Nonprescription Drugs / Q000008:administration & dosage / Q000009:adverse effects*; D010919:Placebos; D011706:Pyloric Antrum / Q000187:drug effects; D012307:Risk Factors; D013270:Stomach / Q000187:drug effects*; D013276:Stomach Ulcer / Q000139:chemically induced
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004366:Nonprescription Drugs; D010919:Placebos; D000082:Acetaminophen; D007660:Ketoprofen