CLINICAL ENDOSCOPIC EVALUATION OF THE GASTRODUODENAL TOLERANCE TO (R)-KETOPROFEN, (R)-FLURBIPROFEN, RACEMIC KETOPROFEN, AND PARACETAMOL - ARANDOMIZED, SINGLE-BLIND, PLACEBO-CONTROLLED TRIAL

Ketoprofen, a nonsteroidal anti inflammatory drug (NSAID) of the 2-ary lpropionic acid class, causes gastroduodenal hemorrhages and erosions in 10-15% of patients. The (S)-enantiomer er exhibits most of the anti -inflammatory properties, with concomitant gastrointestinal toxicity. The (R)-enantiomer, however, was recently found to have analgesic prop erties independent of prostaglandin inhibition. Seventy-two healthy ma le volunteers not receiving NSAIDs, alcohol, or anti-ulcer drugs, were enrolled in a randomized, investigator-blind, placebo-controlled tria l to evaluate the gastroduodenal tolerance of (R)- ketoprofen 100 mg b .i.d., (R)- flurbiprofen 100 mg b.i.d., racemic ketoprofen 100 mg b.i. d., and paracetamol 1,000 mg b.i.d. Gastroduodenal endoscopies at base line and after 2.5 days of dosing were used to detect newly occurring hemorrhages and erosions. Adverse events were also recorded. The incid ence of submucosal hemorrhages was 4/16 in the (R)-ketoprofen group, 5 /16 in the (R)- flurbiprofen group, 12/16 in the racemic ketoprofen gr oup, 1/16 in the paracetamol group, and 1/8 in the placebo group. The incidence of erosions was 2/16 in the (R)- ketoprofen group, 4/16 in t he (R)- flurbiprofen group, 10/16 in the racemic ketoprofen group, 10/ 16 in the paracetamol group, and 2/8 in the placebo group. The differe nces in hemorrhages and erosions among treatments were statistically s ignificant (gastric hemorrhages P = 0.0008; duodenal hemorrhages P = 0 .00062 gastric erosions P = 0.0004; duodenal erosions P = 0.0062, Krus kal-Wallis test). At 110 mg b.i.d., (R)-ketoprofen caused fewer gastro duodenal hemorrhages and erosions than racemic ketoprofen (P = 0.019, P = 0.0112, P = 0.0097, P = 0.0139 for gastric, duodenal hemorrhages a nd gastric, duodenal erosions, respectively). The difference between 1 00 mg b.i.d. (R)- ketoprofen and 100 mg b.i.d (R)- flurbiprofen was no t statistically significant. The dissociation between analgesic and an ti-inflammatory properties for (R)- ketoprofen suggests that it may re present a unique analgesic with a favorable safety profile.