生体膜輸送の分子機構に関する生物薬剤学的研究

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タイトル別名
  • Biopharmaceutical Studies on Molecular Mechanisms of Membrane Transport
  • セイタイ マク ユソウ ノ ブンシ キコウ ニ カンスル セイブツ ヤクザイガクテキ ケンキュウ

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By incorporating the transporter-mediated or receptor-mediated transport process in physiologically based pharmacokinetic models, we succeeded in the quantitative prediction of plasma and tissue concentrations of β-lactam antibiotics, insulin, pentazocine, quinolone antibacterial agents, and inaperizone and digoxin. The author's research on transporter-mediated pharmacokinetics focuses on the molecular and functional characteristics of drug transporters such as oligopeptide transporter, monocarboxylic acid transporter, anion antiporter, organic anion transporters, organic cation/carnitine transporters (OCTNs), and the ATP-binding cassette transporters P-glycoprotein and MRP2. We have successfully demonstrated that these transporters play important roles in the influxes and/or effluxes of drugs in intestinal and renal epithelial cells, hepatocytes, and brain capillary endothelial cells that form the blood-brain barrier. In the systemic carnitine deficiency (SCD) phenotype mouse model, juvenile visceral steatosis (jvs) mouse, a mutation in the OCTN2 gene was found. Furthermore, several types of mutation in human SCD patients were found, demonstrating that OCTN2 is a physiologically important carnitine transporter. Interestingly, OCTNs transport carnitine in a sodium-dependent manner and various cationic drugs transport it in a sodium-independent manner. OCTNs are thought to be multifunctional transporters for the uptake of carnitine into tissue cells and for the elimination of intracellular organic cationic drugs.<br>

収録刊行物

  • 薬学雑誌

    薬学雑誌 122 (12), 1037-1058, 2002-12-01

    公益社団法人 日本薬学会

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