Biochemical Study for Absorption Mechanism of Lipophilic Drug from Intestine to Lymphatic fluid

亲脂性药物肠道至淋巴液吸收机制的生化研究

• 批准号: 07672350
• 负责人: ADACHI Isao
• 金额: $ 0.96万
• 依托单位: TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07672350/
• 关键词: lymphatic absorption; endocytosis; lipophilic drug; Ubidecarenone

Ubidecarenone was employed as a model drug for lipophilic drugs. After drug was administered into the stomach of rats, lymphatic fluid and portal vein blood were collected and subjected to HPLC analysis for drug quantification. Ubidecarenone was found to transfered selectively to lymphatic fluid. When glycerol mono-olate was co-administerd to rats, lymphatic absorption was increased about 3-fold. The absorption of ubidecarenone to lymphatic fluid was suppressed by monensine, endocytosis inhibitor, and it also inhibited the binding of ubidecarenone to intestinal tissue in vitro. Both the facts suggest that endocytosis plays an important role for lymphatic absorption of ubidecarenone. Moreover, 85% of ubidecarenone was found to be in the reduced-form in lymphatic fluid even when the oxidized-form of ubidecarenone was administered. This phenomenon is very precious and important and should be pursued further. Ubidecarenone was found to be reduced by enzyme during the absorption phase and not in the intestine nor in the lymphatic fluid. Enzyme, which is located in the plasma membrane, responsible for this reduction is sensitive against sulfydryl inhibitors.These results imply that the role of ubidecarenone reduction in the lymphatic absorption throught endocytosis should be studied intensively.

甲烯酮被用作亲脂性药物的模型药物。药物施用到大鼠的胃中后，收集淋巴液和门静脉血液，并进行HPLC分析以进行药物定量。发现甲状腺素酮被选择性地转移到淋巴液中。当甘油单酸是共辅助到大鼠时，淋巴吸收会增加约3倍。 Monensine，内吞作用抑制剂抑制了甲状腺素酮对淋巴液的吸收，并且还抑制了甲状腺素酮与体外肠道组织的结合。这两个事实都表明，内吞作用对于甲状腺素酮的淋巴吸收起着重要作用。此外，即使施用氧化甲烯酮的氧化形式，也发现有85％的甲状腺烯酮在淋巴液中的降低中。这种现象非常珍贵和重要，应该进一步追求。发现在吸收阶段而不是在肠道或淋巴液中，甲烯酮被酶降低。位于质膜中的酶对这种还原的负责是对磺酰基抑制剂的敏感性。这些结果表明，应深入研究甲烯酮降低在淋巴吸收中的作用。