Dose-dependent effects of ketoprofen on the human gastric mucosa in comparison with ibuprofen

Background: As non-steroidal anti-inflammatory drugs (NSAIDs) become availa ble for over-the-counter use, it is important to define doses that would no t 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 maximu m dose of ibuprofen (400 mg t.d.s.) licensed for self-medication. Methods: We studied healthy volunteers in a double-blind double-dummy rando mized 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 endosco py at baseline and on the 3rd and 10th day of each dosing period. Ex vivo g astric mucosal prostaglandin (PG) E-2 evoked by vortex mixing was measured by radioimmunoassay. Serum thromboxane was also measured by radioimmunoassa y. Results: Ketoprofen 50 mg t.d.s. suppressed prostaglandin synthesis to a si gnificantly greater extent than ibuprofen and caused significantly more gas troduodenal injury. The profile of prostaglandin synthesis and injury on ke toprofen 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-medi cation, which is likely to be similar to ibuprofen 400 mg t.d.s. in its eff ects on the stomach and duodenum.