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Dose‐dependent effects of ketoprofen on the human gastric mucosa in comparison with ibuprofen
Author(s) -
Mark Donnelly,
Paul Richardson,
C. J. Hawkey,
EM Courtauld,
W. A. Stack
Publication year - 2000
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.2000.00743.x
Subject(s) - ketoprofen , ibuprofen , medicine , radioimmunoassay , crossover study , prostaglandin , stomach , pharmacology , prostaglandin e , thromboxane , anesthesia , gastroenterology , platelet , pathology , alternative medicine , placebo
Background: As non‐steroidal anti‐inflammatory drugs (NSAIDs) become available for over‐the‐counter use, it is important to define doses that would not cause undue gastroduodenal damage during the short periods for which self‐medication with NSAIDs is licensed. Aim: To establish what dose of ketoprofen most closely resembles the maximum dose of ibuprofen (400 mg t.d.s.) licensed for self‐medication. Methods: We studied healthy volunteers in a double‐blind double‐dummy randomized crossover study. Each subject took, over four separate 10‐day dosing periods, ibuprofen 400 mg t.d.s., ketoprofen 12.5 mg t.d.s., ketoprofen 25 mg t.d.s. or ketoprofen 50 mg t.d.s. Mucosal injury was assessed by endoscopy at baseline and on the 3rd and 10th day of each dosing period. Ex vivo gastric mucosal prostaglandin (PG) E 2 evoked by vortex mixing was measured by radioimmunoassay. Serum thromboxane was also measured by radioimmunoassay. Results: Ketoprofen 50 mg t.d.s. suppressed prostaglandin synthesis to a significantly greater extent than ibuprofen and caused significantly more gastroduodenal injury. The profile of prostaglandin synthesis and injury on ketoprofen 12.5 mg t.d.s. most closely resembled that of ibuprofen 400 mg t.d.s. Conclusions: Ketoprofen 12.5 mg t.d.s. is an appropriate dose for self‐medication, which is likely to be similar to ibuprofen 400 mg t.d.s. in its effects on the stomach and duodenum.