非ステロイド性抗炎症薬Ｏｘａｐｒｏｚｉｎの血小板凝集抑制作用

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  • The inhibitory effect of oxaprozin, a new non-steroidal anti-inflammatory drug, on platelet aggregation
  • ヒ ステロイドセイ コウ エンショウヤク Oxaprozin ノ ケッショウバ

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The inhibitory effects of oxaprozin, a new non-steroidal anti-inflammatory drug, on platelet aggregation and prostaglandin (PG) synthetase activity were studied. In arachidonic acid (AA)-induced rabbit platelet aggregation in vitro, oxaprozin exhibited a dose-dependent inhibitory effect, and its median inhibitory concentration was 124.2, μM. The effect of oxaprozin was less potent than that of indomethacin and piroxicam, equipotent as that of aspirin and phenylbutazone, and 2 times as potent as that of ibuprofen. In collagen-induced rat platelet aggregation ex vivo, oxaprozin showed a weak but significant inhibitory effect with oral dose of 300 mg/kg. Indomethacin, aspirin and ibuprofen exhibited an inhibitory effect with 100 mg/kg. Although phenylbutazone also exhibited an inhibitory effect with 300 mg/kg, the effect was more potent than that of oxaprozin. ADP-induced platelet aggregation both in rabbit in vitro and rat ex vivo was not affected by oxaprozin. Moreover, oxaprozin administered orally inhibited dose-dependently AA-induced pulmonary thrombotic mortality in mice, and its median effective dose was 56.4 mg/kg. The effect of oxaprozin was less potent than of sulindac, piroxicam and ibuprofen, equipotent as that of aspirin, and 5 times as potent as that of phenylbutazone. On the other hand, oxaprozin inhibited dose-dependently PG synthetase activity. The inhibitory effect of oxaprozin was less potent than that of indomethacin and piroxicam, almost equipotent as that of ibuprofen, and more potent than that of phenylbutazone and aspirin. These results suggest that oxaprozin, like many other acidic non-steroidal anti-inflammatory drugs, suppresses platelet aggregation by mainly inhibiting PG synthetase activity.

収録刊行物

  • 日本薬理学雑誌

    日本薬理学雑誌 83 (5), 395-400, 1984

    公益社団法人 日本薬理学会

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