薬物の肝胆系移行の速度論的解析 : 担体輸送の重要性

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タイトル別名
  • Kinetic Analysis of Hepatobiliary Transport of Drugs : Importance of Carrier-mediated Transport
  • ヤクブツ ノ カンタンケイ イコウ ノ ソクドロンテキ カイセキ タンタイ ユ

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抄録

The liver is the major organ involved in the metabolism and elimination of xenobiotics. Evaluating accurately hepatic clearance is very important for predicting the pharmacological effect and/or side-effects of drugs, as well as changes in drug disposition during disease. Recently, for many endogenous and exogenous compounds (including drugs), it has been reported that carriermediated transport contributes to hepatic uptake and/or biliary excretion. In particular, primary active transport mechanisms have been shown to be responsible for the biliary excretion of anticancer drugs, endogenous bile acids and organic anions including glutathione and glucuronic acid conjugates. We have found that a rate-limiting step for several drugs in terms of the hepatic clearance was the membrane transport process. For these drugs, such a saturable transport process can be one of the major determinants which influence not only hepatic clearance itself but also disposition (in other words, plasma elimination) in the whole body. We reviewed the carrier-mediated transport mechanisms involved in the hepatic uptake and biliary excretion processes, the multiplicity of transport systems, and further, the physiological meaning of these complex transport systems in the body.

収録刊行物

  • 薬学雑誌

    薬学雑誌 115 (12), 953-977, 1995

    公益社団法人 日本薬学会

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