2013 Fiscal Year Final Research Report
Elucidation of the transporters, and integration research of their molecular entities and activities for the drug transport in the brain and kidneys
| Project/Area Number |
23390034
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Hisamitsu 東京大学, 大学院・薬学系研究科, 助教 (10451858)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Keywords | 薬物動態 / SLCトランスポーター / 腎排泄 / 薬物間相互作用 / 血液脳関門 / 中枢移行性 |
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| Research Abstract |
This study elucidated that MATEs which act as H+/organic cation exchanges mediate the urinary excretion of various drugs, endogenous metabolite (N-methylnicotinamide) and fluorescents in mouse, and that inhibition of MATEs is part of the mechanism underlying the drug-drug interactions in the urinary excretion with cimetidine and trimethoprim. NPT4 mediates facilitated diffusion of various anionic drugs such as diuretics in HEK293 cells. MCT9 is found to be expressed on the basolateral membrane of the proximal tubules. Among the drugs which undergo urinary excretion, OCT2 can recognize only hydrophilic compounds as substrate. MCT9 also acts as organic cation transporter showing substrate specificity distinct from OCT2. Since MCT9 is also expressed in the blood-brain barrier, it is speculated that MCT9 is involved in the disposition of drugs in the central nervous system in addition to the kidney.
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Research Products
(35 results)
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[Journal Article] Effect of coadministration of single and multiple doses of rifampicin on the pharmacokinetics of fexofenadine enantiomers in healthy subjects2013
Author(s)
Kusuhara H, Miura M, Yasui-Furukori N, Yoshida K, Akamine Y, Yokochi M, Fukizawa S, Ikejiri K, Kanamitsu K, Uno T, Sugiyama Y
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Journal Title
Drug Metab Dispos
Volume: 41
Pages: 206-13
Peer Reviewed
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[Journal Article] N-methylnicotinamide is an endogenous probe for evaluation of drug-drug interactions involving multidrug and toxin extrusions (MATE1 and MATE2-K)2012
Author(s)
Ito S, Kusuhara H, Kumagai Y, Moriyama Y, Inoue K, Kondo T, Nakayama H, Horita S, Tanabe K, Yuasa H, Sugiyama Y
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Journal Title
Clin Pharmacol Ther
Volume: 92
Pages: 635-41
Peer Reviewed
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