title: Clinical endoscopic evaluation of the gastroduodenal tolerance to (R)- ketoprofen, (R)- flurbiprofen, racemic ketoprofen, and paracetamol: a randomized, single-blind, placebo-controlled trial.
abstract: Ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID) of the 2-arylpropionic acid class, causes gastroduodenal hemorrhages and erosions in 10-15% of patients. The (S)- enantiomer exhibits most of the anti-inflammatory properties, with concomitant gastrointestinal toxicity. The (R)- enantiomer, however, was recently found to have analgesic properties independent of prostaglandin inhibition. Seventy-two healthy male volunteers not receiving NSAIDs, alcohol, or anti-ulcer drugs, were enrolled in a randomized, investigator-blind, placebo-controlled trial 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 baseline and after 2.5 days of dosing were used to detect newly occurring hemorrhages and erosions. Adverse events were also recorded. The incidence of submucosal hemorrhages was 4/16 in the (R)- ketoprofen group, 5/16 in the (R)- flurbiprofen group, 12/16 in the racemic ketoprofen group, 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 the (R)- flurbiprofen group, 10/16 in the racemic ketoprofen group, 0/16 in the paracetamol group, and 2/8 in the placebo group. The differences in hemorrhages and erosions among treatments were statistically significant (gastric hemorrhages P = 0.0008; duodenal hemorrhages P = 0.00062; gastric erosions P = 0.0004; duodenal erosions P = 0.0062, Kruskal-Wallis test). At 100 mg b.i.d., (R)- ketoprofen caused fewer gastroduodenal hemorrhages and erosions than racemic ketoprofen (P = 0.019, P = 0.0112, P = 0.0097, P = 0.0139 for gastric, duodenal hemorrhages and gastric, duodenal erosions, respectively). The difference between 100 mg b.i.d. (R)- ketoprofen and 100 mg b.i.d. (R)- flurbiprofen was not statistically significant. The dissociation between analgesic and anti-inflammatory properties for (R)- ketoprofen suggests that it may represent a unique analgesic with a favorable safety profile.
authors.affiliation: Sepracor, Inc., Marlborough, MA 01752, USA.
authors.forename: T P
authors.initials: TP
authors.lastname: Jerussi
authors.forename: J F
authors.initials: JF
authors.lastname: Caubet
authors.forename: J E
authors.initials: JE
authors.lastname: McCray
authors.forename: D A
authors.initials: DA
authors.lastname: Handley
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000700:Analgesics / Q000009:adverse effects*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D004378:Duodenal Diseases / Q000139:chemically induced*; D004381:Duodenal Ulcer / Q000139:chemically induced*; D016099:Endoscopy, Gastrointestinal; D005480:Flurbiprofen / Q000009:adverse effects*; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced*; D006801:Humans; D007660:Ketoprofen / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D016037:Single-Blind Method; D013237:Stereoisomerism; D013272:Stomach Diseases / Q000139:chemically induced*; D013276:Stomach Ulcer / Q000139:chemically induced*
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010919:Placebos; D000082:Acetaminophen; D005480:Flurbiprofen; D007660:Ketoprofen