非ステロイド性抗炎症剤による消化管障害の, ラットにおける比較検討

概要

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Gastrointestinal damage induced by oral administration of non-steroidal anti-inflammatory agents (flurbiprofen, phenylbutazone, indomethacin and acetylsalicylic acid) was examined. Wistar male rats in the fasting state for 16 hr received the agent orally. The dose was determined from the equation : D=ED_<50>×K_i, where ED_<50> is the median inhibitory dose on carrageenin edema in the rat paw and K_i is the coefficient. Rats were sacrificed without anesthesia by cutting both common carotid arteries at 6 hr after drug administration and gastrointestinal specimens were visually examined. Cumulative method was applied for statistical analysis of the number of rats in each grade of the damage. On the basis of the statistical data, availability (balance between effect and hazard) of the tested drugs was discussed, and safety margins and their confidence limits at ED_<50> of the drugs were estimated. In further study, median ulcerogenic dose (UD_<50>) and UD_<50>/ED_<50> ratio of each tested drug were calculated. Availability evaluated on statistical consideration decreased in the order of flurbiprofen, phenylbutazone, indomethacin, and acetylsalicylic acid.
公益社団法人日本薬学会の論文
1978-08-25