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生体膜輸送の分子機構に関する生物薬剤学的研究 Biopharmaceutical studies on molecular mechanisms of membrane transport Tsuji, Akira 21465 10019664 10019664 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 defficiency (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. © 2002 The Pharmaceutical Society of Japan. 金沢大学薬学部 金沢大学医薬保健研究域薬学系 journal article 日本薬学会 2002-12-01 VoR application/pdf 藥學雜誌 = Yakugaku Zasshi 12 122 1307 1058 AN00241525 0031-6903 https://kanazawa-u.repo.nii.ac.jp/record/15318/files/PH-PR-TSUJI-A-1037.pdf http://hdl.handle.net/2297/14413 https://kanazawa-u.repo.nii.ac.jp/records/15318 jpn 10.1248/yakushi.122.1037 http://dx.doi.org/10.1248/yakushi.122.1037