癌化学療法における薬物体内動態解析に関する研究

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タイトル別名
  • Pharmacokinetic Study of Cancer Chemotherapy
  • ガン カガク リョウホウ ニ オケル ヤクブツタイナイ ドウタイ カイセキ ニ カンスル ケンキュウ

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  We reported that the rate of conversion of lactone to carboxylate forms of irinotecan (CPT-11) and its metabolites plays a major role in the biliary excretion of these compounds. Sulfobromophthalein partially inhibited the secretion of SN-38-glucronide into the gastrointestinal lumen, whereas little change was seen in that of active metabolite SN-38. Co-administration of sulphobromophthalein with CPT-11 might lower the late-onset gastrointestinal toxicity observed during treatment with CPT-11 without lowering anticancer activity. In the ileum, the level of transport in the direction form the serosal layer to mucosal layer was significantly greater than that in the direction form the mucosal layer to serosal layer, whereas a significant difference was not observed in the jejunum. This secretory transport required metabolic energy was diminished by sulfobromophthalein. A specific transport system plays a major role in the secretion of SN-38 and that this secretory transport system predominantly exists in the ileum. Uptake of SN-38 was significantly reducted at 4°C. Baicalin inhibited the uptake of SN-38. A specific transport system mediates the uptake of SN-38 across the apical membrane in Caco-2 cells. Inhibition of this transporter would be a useful means for reducing late-onset diarrhea.<br>

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  • 薬学雑誌

    薬学雑誌 126 (9), 723-735, 2006-09-01

    公益社団法人 日本薬学会

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