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2010 Fiscal Year Final Research Report

PHARMACOKINETICS IN THE PATIENTS WITH METABOLIC SYNDROME AND APPLICATION FOR PHARMACOTHERAPY

Research Project

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Project/Area Number 20249036
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied pharmacology
Research InstitutionKyoto University

Principal Investigator

INUI Ken-ichi  Kyoto University, 医学研究科, 名誉教授 (70034030)

Co-Investigator(Kenkyū-buntansha) KATSURA Toshiya  京都大学, 医学研究科, 准教授 (10283615)
MASUDA Satoshiro  京都大学, 医学研究科, 講師 (90303825)
TERADA Tomohiro  京都大学, 医学研究科, 薬剤部副薬剤部長 (10324641)
YONEZAWA Atsushi  京都大学, 医学研究科, 助教 (90452341)
Project Period (FY) 2008 – 2010
Keywords薬学 / 薬剤反応 / 薬物トランスポータ / 転写因子 / 核内受容体 / メトホルミン
Research Abstract

Drug response is likely altered in the patient with metabolic syndrome. The present results indicated that the expression levels of drug transporters were varied, and pharmacokinetics was changed in several diseases. Especially, we clearly revealed that an efflux transporter MATE1 could influence the sensitivities of anti-diabetic drug metformin and anti-cancer drug cisplatin. These outcomes can lead to the optimized pharmacotherapy in metabolic syndrome patients.

  • Research Products

    (48 results)

All 2011 2010 2009 2008 Other

All Journal Article (29 results) (of which Peer Reviewed: 29 results) Presentation (18 results) Remarks (1 results)

  • [Journal Article] Effects of metabolic acidosis on expression levels of renal drug transporters.2011

    • Author(s)
      Gaowa A, Motohashi H, Katsura T, Inui K.
    • Journal Title

      Pharm Res 28

      Pages: 1023-1030

    • Peer Reviewed
  • [Journal Article] Organic cation transporter OCT/SLC22A and H^+/organic cation antiporter MATE/SLC47A are key molecules for nephrotoxicity of platinum agents.2011

    • Author(s)
      Yonezawa A, Inui K.
    • Journal Title

      Biochem Pharmacol 81

      Pages: 563-568

    • Peer Reviewed
  • [Journal Article] Maternal riboflavin deficiency, resulting in transient neonatal-onset glutaric aciduria Type 2, is caused by a microdeletion in the riboflavin transporter gene GPR172B.2010

    • Author(s)
      Ho G, Yonezawa A, Masuda S, Inui K, 以下7名
    • Journal Title

      Hum Mutat 32

      Pages: E1976-1984

    • Peer Reviewed
  • [Journal Article] ABCG2 421C>A polymorphism and high exposure of sunitinib in a patient with renal cell carcinoma.2010

    • Author(s)
      Mizuno T, Terada T, Kamba T, Fukudo M, Katsura T, Nakamura E, Ogawa O, Inui K.
    • Journal Title

      Ann Oncol 21

      Pages: 1382-1383

    • Peer Reviewed
  • [Journal Article] Topical insulin-like growth factor 1 treatment using gelatin hydrogels for glucocorticoid-resistant sudden sensorineural hearing loss : a prospective clinical trial.2010

    • Author(s)
      Nakagawa T, Sakamoto T, Hiraumi H, Kikkawa YS, Yamamoto N, Hamaguchi K, Ono K, Yamamoto M, Tabata Y, Teramukai S, Tanaka S, Tada H, Onodera R, Yonezawa A, Inui K, Ito J.
    • Journal Title

      BMC Med 8

      Pages: 76

    • Peer Reviewed
  • [Journal Article] Disruption of multidrug and toxin extrusion MATE1 potentiates cisplatin-induced nephrotoxicity.2010

    • Author(s)
      Nakamura T, Yonezawa A, Hashimoto S, Katsura T, Inui K.
    • Journal Title

      Biochem Pharmacol 80

      Pages: 1762-1767

    • Peer Reviewed
  • [Journal Article] Impact of Cyclin B2 and Cell division cycle 2 on tubular hyperplasia in progressive chronic renal failure rats.2010

    • Author(s)
      Nishihara K, Masuda S, Nakagawa S, Yonezawa A, Ichimura T, Bonventre JV, Inui K.
    • Journal Title

      Am J Physiol Renal Physiol 298

      Pages: F923-934

    • Peer Reviewed
  • [Journal Article] Hepatitis C virus-related cirrhosis is a major determinant of the expression levels of hepatic drug transporters.2010

    • Author(s)
      Ogasawara K, Terada T, Katsura T, Hatano E, Ikai I, Yamaoka Y, Inui K.
    • Journal Title

      Drug Metab Pharmacokinet 25

      Pages: 190-199

    • Peer Reviewed
  • [Journal Article] Heterozygous variants of multidrug and toxin extrusions (MATE1 and MATE2-K) have little influence on the disposition of metformin in diabetic patients.2010

    • Author(s)
      Toyama K, Yonezawa A, Tsuda M, Masuda S, Yano I, Terada T, Osawa R, Katsura T, Hosokawa M, Fujimoto S, Inagaki N, Inui K.
    • Journal Title

      Pharmacogenet Genomics 20

      Pages: 135-138

    • Peer Reviewed
  • [Journal Article] Reduced renal clearance of a zwitterionic substrate cephalexin in MATE1-deficient mice.2010

    • Author(s)
      Watanabe S, Tsuda M, Terada T, Katsura T, Inui K.
    • Journal Title

      J Pharmacol Exp Ther 334

      Pages: 651-656

    • Peer Reviewed
  • [Journal Article] Identification and comparative functional characterization of a new human riboflavin transporter hRFT3 expressed in the brain.2010

    • Author(s)
      Yao Y, Yonezawa A, Yoshimatsu H, Masuda S, Katsura T, Inui K.
    • Journal Title

      J Nutr 140

      Pages: 1220-1226

    • Peer Reviewed
  • [Journal Article] Immunosuppressive effects of tacrolimus on macrophages ameliorate experimental colitis.2010

    • Author(s)
      Yoshino T, Nakase H, Honzawa Y, Matsumura K, Yamamoto S, Takeda Y, Ueno S, Uza N, Masuda S, Inui K, Chiba T.
    • Journal Title

      Inflamm Bowel Dis 16

      Pages: 2022-2033

    • Peer Reviewed
  • [Journal Article] Impact of regulatory polymorphisms in organic anion transporter genes in the human liver.2009

    • Author(s)
      Aoki M, Terada T, Ogasawara K, Katsura T, Hatano E, Ikai I, Inui K.
    • Journal Title

      Pharmacogenet Genomics 19

      Pages: 647-656

    • Peer Reviewed
  • [Journal Article] Identification of multidrug and toxin extrusion (MATE1 and MATE2-K) variants with complete loss of transport activity.2009

    • Author(s)
      Kajiwara M, Terada T, Ogasawara K, Iwano J, Katsura T, Fukatsu A, Doi T, Inui K.
    • Journal Title

      J Hum Genet 54

      Pages: 40-46

    • Peer Reviewed
  • [Journal Article] Transport of guanidine compounds by human organic cation transporters, hOCT1 and hOCT2.2009

    • Author(s)
      Kimura N, Masuda S, Katsura T, Inui K.
    • Journal Title

      Biochem Pharmacol 77

      Pages: 1429-1436

    • Peer Reviewed
  • [Journal Article] SLCO4C1 transporter eliminates uremic toxins and attenuates hypertension and renal inflammation.2009

    • Author(s)
      Toyohara T, Suzuki T, Morimoto R, Akiyama Y, Souma T, Shiwaku HO, Takeuchi Y, Mishima E, Abe M, Tanemoto M, Masuda S, Kawano H, Maemura K, Nakayama M, Sato H, Mikkaichi T, Yamaguchi H, Fukui S, Fukumoto Y, Shimokawa H, Inui K, 以下11名
    • Journal Title

      J Am Soc Nephrol 20

      Pages: 2546-2555

    • Peer Reviewed
  • [Journal Article] Targeted disruption of the multidrug and toxin extrusion 1 (mate1) gene in mice reduces renal secretion of metformin.2009

    • Author(s)
      Tsuda M, Terada T, Mizuno T, Katsura T, Shimakura J, Inui K.
    • Journal Title

      Mol Pharmacol 75

      Pages: 1280-1286

    • Peer Reviewed
  • [Journal Article] Involvement of human multidrug and toxin extrusion 1 in the drug interaction between cimetidine and metformin in renal epithelial cells.2009

    • Author(s)
      Tsuda M, Terada T, Ueba M, Sato T, Masuda S, Katsura T, Inui K.
    • Journal Title

      J Pharmacol Exp Ther 329

      Pages: 185-191

    • Peer Reviewed
  • [Journal Article] Kidney-specific expression of human organic cation transporter 2 (OCT2/SLC22A2) is regulated by DNA methylation.2008

    • Author(s)
      Aoki M, Terada T, Kajiwara M, Ogasawara K, Ikai I, Ogawa O, Katsura T, Inui K.
    • Journal Title

      Am J Physiol Renal Physiol 295

      Pages: F165-170

    • Peer Reviewed
  • [Journal Article] Adaptive responses of renal organic anion transporter 3 (OAT3) during cholestasis.2008

    • Author(s)
      Chen J, Terada T, Ogasawara K, Katsura T, Inui K.
    • Journal Title

      Am J Physiol Renal Physiol 295

      Pages: F247-252

    • Peer Reviewed
  • [Journal Article] Regulation of basal core promoter activity of human organic cation transporter 1(OCT1/SLC22A1).2008

    • Author(s)
      Kajiwara M, Terada T, Asaka J, Aoki M, Katsura T, Ikai I, Inui K.
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol 295

      Pages: G1211-1216

    • Peer Reviewed
  • [Journal Article] Thyroid hormone regulates the expression and function of P-glycoprotein in Caco-2 cells.2008

    • Author(s)
      Nishio N, Katsura T, Inui K.
    • Journal Title

      Pharm Res 25

      Pages: 1037-1042

    • Peer Reviewed
  • [Journal Article] Analysis of regulatory polymorphisms in organic ion transporter genes (SLC22A) in the kidney.2008

    • Author(s)
      Ogasawara K, Terada T, Motohashi H, Asaka J, Aoki M, Katsura T, Kamba T, Ogawa O, Inui K.
    • Journal Title

      J Hum Genet 53

      Pages: 607-614

    • Peer Reviewed
  • [Journal Article] Inhibitory effect of zinc on the absorption of beta-lactam antibiotic ceftibuten via the peptide transporters in rats.2008

    • Author(s)
      Okamura M, Terada T, Katsura T, Inui K.
    • Journal Title

      Drug Metab Pharmacokinet 23

      Pages: 464-468

    • Peer Reviewed
  • [Journal Article] Regulatory mechanism governing the diurnal rhythm of intestinal H^+/peptide cotransporter 1 (PEPT1).2008

    • Author(s)
      Saito H, Terada T, Shimakura J, Katsura T, Inui K.
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol 295

      Pages: G395-402

    • Peer Reviewed
  • [Journal Article] Transcellular transport of organic cations in double-transfected MDCK cells expressing human organic cation transporters hOCT1/hMATE1 and hOCT2/hMATE1.2008

    • Author(s)
      Sato T, Masuda S, Yonezawa A, Tanihara Y, Katsura T, Inui K.
    • Journal Title

      Biochem Pharmacol 76

      Pages: 894-903

    • Peer Reviewed
  • [Journal Article] Significance of organic cation transporter 3 (SLC22A3) expression for the cytotoxic effect of oxaliplatin in colorectal cancer.2008

    • Author(s)
      Yokoo S, Masuda S, Yonezawa A, Terada T, Katsura T, Inui K.
    • Journal Title

      Drug Metab Dispos 36

      Pages: 2299-2306

    • Peer Reviewed
  • [Journal Article] Identification and functional characterization of a novel human and rat riboflavin transporter, RFT1.2008

    • Author(s)
      Yonezawa A, Masuda S, Katsura T, Inui K.
    • Journal Title

      Am J Physiol Cell Physiol 295

      Pages: C632-641

    • Peer Reviewed
  • [Journal Article] Importance of the Multidrug and Toxin Extrusion MATE/SLC47A Family to Pharmacokinetics, Pharmacodynamics /Toxicodynamics and Pharmacogenomics.

    • Author(s)
      Yonezawa A, Inui K.
    • Journal Title

      Br J Pharmacol (in press)

    • Peer Reviewed
  • [Presentation] H^+/有機カチオンアンチポータMATEの遺伝子多型によるメトホルミンの体内動態変化2010

    • Author(s)
      遠山佳奈
    • Organizer
      第31回臨床薬理学会年会
    • Place of Presentation
      国立京都国際会館(京都市)
    • Year and Date
      2010-12-01
  • [Presentation] H^+/有機カチオンアンチポータMATE1ノックアウトマウスにおけるシスプラチン誘発腎毒性の増強2010

    • Author(s)
      中村高規
    • Organizer
      第32回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      富山国際会議場(富山市)
    • Year and Date
      2010-11-29
  • [Presentation] Involvement of MATE1 in renal tubular secretion of varenicline.2010

    • Author(s)
      梶原望渡
    • Organizer
      Pharmaceutical Sciences World Congress 2010
    • Place of Presentation
      ニューオーリンズ(アメリカ)
    • Year and Date
      2010-11-14
  • [Presentation] Flux of platinum agents by MATE2-K rather than MATE1 in the double transfectants with basolateral OCT2 in MDCK monolayers.2010

    • Author(s)
      Sato T
    • Organizer
      Pharmaceutical Sciences World Congress 2010
    • Place of Presentation
      ニューオーリンズ(アメリカ)
    • Year and Date
      2010-11-14
  • [Presentation] OCT2/MATE2-K double transfectant, as an in vitro model of renal handling of cationic drugs in human kidney.2010

    • Author(s)
      Sato T
    • Organizer
      日本薬物動態学会第25年会
    • Place of Presentation
      大宮ソニックシティ(大宮市)
    • Year and Date
      2010-10-06
  • [Presentation] Multidrug and toxin extrusion 1 mediated tubular secretion of varenicline.2010

    • Author(s)
      梶原望渡
    • Organizer
      日本薬物動態学会第25年会
    • Place of Presentation
      大宮ソニックシティ(大宮市)
    • Year and Date
      2010-10-06
  • [Presentation] Interaction between guanidino compounds and human multidrug and toxin extrusion (hMATE)1 and hMATE2-K.2010

    • Author(s)
      Motoyama S
    • Organizer
      日本薬物動態学会第25年会
    • Place of Presentation
      大宮ソニックシティ(大宮市)
    • Year and Date
      2010-10-06
  • [Presentation] PREDOMINANT ROLE OF H^+/ORGANIC CATION ANTIPORTER MATE1/SLC47A1 IN THE RENAL TUBULAR SECRETION OF METFORMIN AND CEPHALEXIN.2010

    • Author(s)
      Inui K
    • Organizer
      9th International Meeting of International Society for the Study of Xenobiotics
    • Place of Presentation
      イスタンブール(トルコ)
    • Year and Date
      2010-09-05
  • [Presentation] シスプラチンの腎毒性発現におけるH^+/有機カチオンアンチポータMATE1の役割2010

    • Author(s)
      中村高規
    • Organizer
      日本薬剤学会第25年会
    • Place of Presentation
      あわぎんホール徳島県郷土文化会館(徳島市)
    • Year and Date
      2010-05-12
  • [Presentation] 両性イオン型薬物セファレキシンの腎排泄におけるMATE1の役割2010

    • Author(s)
      渡部辰悟
    • Organizer
      日本薬剤学会第25年会
    • Place of Presentation
      あわぎんホール徳島県郷土文化会館(徳島市)
    • Year and Date
      2010-05-12
  • [Presentation] 生体肝移植術後のタクロリムス体内動態に及ぼす移植部位の影響2010

    • Author(s)
      木村匡宏
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山コンベンションセンター(岡山県)
    • Year and Date
      2010-03-28
  • [Presentation] 慢性腎不全に対する新規治療標的としてのmTOR経路2009

    • Author(s)
      中川俊作
    • Organizer
      第3回次世代を担う若手医療薬科学シンポジウム
    • Place of Presentation
      九州大学病院地区コラボステーション(福岡県)
    • Year and Date
      2009-11-15
  • [Presentation] Roles of the mTOR pathway on progressive tubular dysfunction in chronic renal failure rats.2009

    • Author(s)
      中川俊作
    • Organizer
      BioMedical Transporters 2009
    • Place of Presentation
      シーパークコングレスセンター(トゥーン、スイス連邦)
    • Year and Date
      2009-08-12
  • [Presentation] 腎尿細管薬物トランスポータの病態生理学的役割2008

    • Author(s)
      増田智先
    • Organizer
      第23回日本薬物動態学会年会
    • Place of Presentation
      熊本市民会館(熊本県)
    • Year and Date
      2008-10-30
  • [Presentation] 薬剤業務の科学的基盤の確立と薬物治療への展開2008

    • Author(s)
      乾賢一
    • Organizer
      日本薬剤学会第23年会
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Year and Date
      2008-05-21
  • [Presentation] ヒト有機カチオントランスポータ(hOCT1)の転写調節機構2008

    • Author(s)
      梶原望渡
    • Organizer
      日本薬剤学会第23年会
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Year and Date
      2008-05-20
  • [Presentation] プロモーター領域のメチル化によるヒトOCT2の腎特異的な発現制御2008

    • Author(s)
      青木雅世
    • Organizer
      日本薬剤学会第23年会
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Year and Date
      2008-05-20
  • [Presentation] 腎臓の発達過程における有機アニオントランスポータの発現変動2008

    • Author(s)
      関根寛子
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山コンベンションセンター(岡山県)
    • Year and Date
      2008-05-20
  • [Remarks] ホームページ等

    • URL

      http://www.kuhp.kyoto-u.ac.jp/?yakuzai/main.htm

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Published: 2012-01-26   Modified: 2016-04-21  

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