薬理と治療

Abstract

Antithrombotic therapy takes a central role of the treatment for apoplexy, cardiac disorderand peripheral arterial disease. However, recent clinical studies suggested a risk of gastricadverse reaction on the concomitant use of antithrombotic drugs with nonsteroidal antiinflammatorydrugs（NSAIDs）. In the present study, we used indomethacin as a conventionalNSAID and investigated the adverse effects of anti−platelet drug clopidogrel, a P2Y12 receptorantagonist, on gastric antral ulcers induced by indomethacin in rats, and further examinedthe effects of antisecretory drugs and rebamipide on the antral ulcers induced by indomethacinplus clopidogrel. Male SD rats fasted for 24 hr were refed for 1hr, and subsequently administeredindomethacin（30 mg／kg）s. c. 1 hr after refeeding. Six hours later, the animals werekilled and the stomachs were examined for non−hemorrhagic and hemorrhagic lesions,separately. Clopidogrel（3onof MPO activity. These results suggest that clopidogrel, the anti−platelet drug,aggravates the severity of NSAID−induced antral ulcers in refed rats, especially converting from non−hemorrhagic lesions into hemorrhagic ones. Rebamipide is useful for preventingthe adverse reaction in the antral mucosa caused by the co−administration of NSAID and theantiplatelet drug.（Jpn Pharmacol Ther 2008；36：1007−15）KEY WORDS Indomethacin, Antral ulcer, Clopidogrel, Rebamipide, Rat