Interaction Between NSAIDs and Steroid in Rat Stomach
- Hirofumi KataokaAffiliated withOsaka Research Laboratory, Sawai Pharmaceutical Co., LTD.
- , Yukiko HorieAffiliated withOsaka Research Laboratory, Sawai Pharmaceutical Co., LTD.
- , Rika KoyamaAffiliated withOsaka Research Laboratory, Sawai Pharmaceutical Co., LTD.
- , Seiichi NakatsugiAffiliated withOsaka Research Laboratory, Sawai Pharmaceutical Co., LTD.
- , Masumi FurukawaAffiliated withOsaka Research Laboratory, Sawai Pharmaceutical Co., LTD.
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The relative risk of development of peptic ulcer with the use of nonsteroidal antiinflammatory drugs (NSAIDs) has been reported to increase when these drugs are administered in combination with steroids. We investigated the ulcerogenic potential of a combination of NSAIDs and steroids in rats and the underlying pathogenic mechanisms. Indomethacin alone produced gastric lesions, and the severity of the lesions markedly increased with concomitant administration of prednisolone. However, nimesulide, even in excessive doses, did not produce any gastric lesions, regardless of concomitant administration with prednisolone. Furthermore, we showed that the ulcerogenic potential of indomethacin administered in combination with prednisolone may be related to the induction of physiological changes, such as endogenous prostaglandin deficiency, an increase in neutrophil activation, and gastric hypermotility, by indomethacin and alteration of normal epithelial renewal by the steroid. These results suggest that the ulcerogenic potential of preferential a COX-1 inhibitor increases following concomitant administration with a steroid, whereas, nimesulide, a preferential COX-2 inhibitor, is nonulcerogenic, even when administered concomitantly with a steroid, and is therefore a clinically useful antiinflammatory agent.
- Interaction Between NSAIDs and Steroid in Rat Stomach
Digestive Diseases and Sciences
Volume 45, Issue 7 , pp 1366-1375
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- Kluwer Academic Publishers-Plenum Publishers
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- drug interaction
- gastric lesion
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