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Studies on the urinary assay of CYP-mediated endogenous corticosteroid metabolites with a LC-MS method

Research Project

Project/Area Number 18590542
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory medicine
Research InstitutionMeiji Pharmaceutical University

Principal Investigator

ECHIZEN Hirotoshi  Meiji Pharmaceutical University, 薬学部, 教授 (00191924)

Co-Investigator(Kenkyū-buntansha) OHNISHI Akihiro  東京慈恵会医科大学, 医学部, 助教授 (00194225)
Project Period (FY) 2006 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,360,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥660,000)
Fiscal Year 2009: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2008: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywords薬物代謝 / 個人差 / ステロイドホルモン / LC-MS / ステロイド
Research Abstract

Interindividual variability of the drug metabolizing enzyme activity is associated with those of drug responses and adverse drug reactions. Recent advances in molecular biology have made it possible to account for a part of interindividual variability of important drug metabolizing enzymes, particularly cytochrome P-450s (CYPs) in the light of pharmacogenomics. Nevertheless, it has also become evident that a large interindividual variability still exists in subjects or patients having none of the previously known loss-of-function SNPs in the respective CYP isoforms. Thus, there is a surge of interest to reappraise for assessing CYP isoform activity as phenotype individually. We have previously reported that in vivo CYP3A4 activity may be assessed by urinary excretion of 6β-hydroxycortisol, a CYP3A4 metabolite of adrenal cortisol, or its metabolic ratio of cortisol. In order to extend this idea to other steroid hormones which are thought to be metabolized by different CYP isoforms, we aimed to establish a comprehensive assay method using HPLC-UV and LC-MS. We have established a simultaneous assay method for urinary 2- and 4-hydroxyestradiol and 17-hydroxyprogesterone, of which metabolism are associated with CYP1A2 and CYP2C19, respectively, with an HPLC-UV method as a preliminary study. We found that there is a large interindividual variability in the urinary excretion of those sex steroid metabolites, indicating that there is a good chance to measure interindividual variability of the these CYP activities. Then, we advanced our study to establish a LC-MS method. We consider that this method would be useful for a population study where a large number of clinical samples are to be assayed.

Report

(6 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report   Self-evaluation Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (28 results)

All 2010 2009 2008 2007 2006 Other

All Journal Article (20 results) (of which Peer Reviewed: 14 results) Presentation (4 results) Book (3 results) Remarks (1 results)

  • [Journal Article] Urinary Lipocalin-Type Prostaglandin D Synthase : A Potential Marker for Early Gentamicin-Induced Renal Damage?2009

    • Author(s)
      Nakayama H, Echizen H, et al.
    • Journal Title

      Ther Drug Monit 32

      Pages: 126-130

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Novel Microsatellite Polymorphism of Sodium Channel β1-Subunit Gene(SCN1B)May Underlie Abnormal Cardiac Excitation Manifested by Coved-type ST-elevation Compatible With Brugada Syndrome in Japanese2009

    • Author(s)
      Ogawa R, Kishi R, Takagi A, Sakaue I, Takahashi H, Matsumoto N, Echizen H
    • Journal Title

      Int J Clin Pharmacol Ther 48

      Pages: 109-119

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Urinary Lipocalin Type Prosta- glandin D Synthase : A Potential Marker for Early Gentamicin-Induced Renal Damage?2009

    • Author(s)
      Nakayama H, Echizen H, Gomi T, Shibuya Y, Nakamura Y, Nakano K, Arashi H, Ohnishi S, Tanaka M, Orii T
    • Journal Title

      Ther Drug Monit 32

      Pages: 126-130

    • Related Report
      2008 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] Urinary Lipocalin-Type Prostaglandin D Synthase : A Potential Marker for Early Gentamicin-Induced Renal Damage?2009

    • Author(s)
      Nakayama H, Echizen H, Gomi T, Shibuya Y, Nakamura Y, Nakano K, Arashi H, Ohnishi S, Tanaka M, Orii T
    • Journal Title

      Ther Drug Monit 32

      Pages: 126-130

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduced vancomycin clearance despite unchanged creatinine clearance in patients treated with vancomycin for longer than 4 weeks2008

    • Author(s)
      Nakayama H, Echizen H, Tanaka M, Sato M, Orii T
    • Journal Title

      Ther Drug Monit 30

      Pages: 103-107

    • Related Report
      2008 Annual Research Report 2008 Self-evaluation Report 2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bioequivalence studies between 0.5, 1, and 5 mg warfarin potassium tablets of new formula and those of standard formula2008

    • Author(s)
      Dochiguchi Y, Shiba S, Masuda Y, Kurihara Y, Hasegawa S, Echizen H
    • Journal Title

      Jpn Pharmacol Ther 36

      Pages: 401-409

    • Related Report
      2008 Annual Research Report 2008 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] Proteomic & Transcriptomic Analyses of Retinal Pigment Epithelial Cells Exposed t-o REF-1/TFPI-2, a Growth Promoting Factor2007

    • Author(s)
      Shibuya M, Okamoto H, Nozawa T, Utsumi J, Reddy VN, Echizen H, Tanaka Y, Iwata T.
    • Journal Title

      Invest Ophthalmol Vis Sci 48

      Pages: 516-521

    • Related Report
      2008 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] A meta-analysis on the risk of developing malignancy associated with use of immunosuppressive agents in patients with inflammatory bowel disease2007

    • Author(s)
      Masunaga Y, Ohno K, Ogawa R, Hashiguchi M, Echizen H, Ogata H
    • Journal Title

      Ann Pharmacother 41

      Pages: 21-28

    • Related Report
      2008 Self-evaluation Report 2006 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of low-dose macrolide antibiotics on theophylline disposition in pediatric patients2007

    • Author(s)
      Abe Y, Nanri Y, Oto H, Kitabayashi T, Watanabe S, Odajima Y, Itabashi K, Takahashi H, Echizen H
    • Journal Title

      日本小児呼吸器疾患学会誌 18

      Pages: 7-13

    • NAID

      10019544744

    • Related Report
      2008 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] Proteomic & Transcriptomic Analyses of Retinal Pigment Epithelial Cells Exposed t-o REF-1/TFPI-2,a Growth Promoting Factor2007

    • Author(s)
      Shibuya M, Okamoto H, Nozawa T, Utsumi J, Reddy VN, Echizen H, Tanaka Y, Iwata T.
    • Journal Title

      Invest Ophthalmol Vis Sci 48

      Pages: 516-521

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A meta-analysis on the risk of developing malignancy associated with use of immunosunnressive agents in natients with inflammatory bowel disease2007

    • Author(s)
      Masunaga Y, Ohno K, Ogawa R, Hashiguchi M, Echizen H, Ogata H
    • Journal Title

      Ann Pharmacother 41

      Pages: 21-28

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of low-dose macrolide antibiotics on the ophylline disposition in pediatric patlents2007

    • Author(s)
      Abe Y, Nanri Y, Oto H, Kitabayashi T, Watanabe S, Odajima Y, Itabashi K, Takahashi H, Echizen H
    • Journal Title

      日本小児呼吸器疾患学会誌 18

      Pages: 7-13

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Proteomic & Transcriptomic Analyses of Retinal Pigment Epithelial Cells Exposed to REF-1/TFPI-2, a Growth Promoting Factor2007

    • Author(s)
      Shibuya M, Okamoto H, Nozawa T, Utsumi J, Reddy VN, Echizen H, Tanaka Y, Iwata T.
    • Journal Title

      Invest Ophthalmol Vis Sci 48

      Pages: 516-521

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Different contributions of polymorphisms in VKORC1 and CYP2C9 to intra-and inter-population differences in maintenance dose of warfarin in Japanese, Caucasians and African Americans.2006

    • Author(s)
      Takahashi, H, Wilkinson, GR, Nutescu, EA, Morita, T, Ritchie, M, Scordo, MG, Pengo, V, Barban, M, Padrini, R, Ieiri I, Otsubo, K, Kashima T, Kimura S, Kijima S, Echizen H
    • Journal Title

      Pharmacogenetics & Genomics 16

      Pages: 101-110

    • Related Report
      2009 Final Research Report
  • [Journal Article] Different contributions of polymorphisms in VKORC1 and CYP2C9 to intra- and inter-population differences in maintenance dose of warfarin in Japanese, Caucasians and African Americans2006

    • Author(s)
      Takahashi, H, Wilkinson, GR, Nutescu, EA, Morita, T, Ritchie, M, Scordo, MG, Pengo, V, Barban, M, Padrini, R, Ieiri I, Otsubo, K, Kashima T, Kimura S, Kijima S, Echizen H
    • Journal Title

      Pharmacogenetics &amp ; Genomics 16

      Pages: 101-110

    • Related Report
      2008 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] Population Pharmacokinetic and Pharmacodynamic Analysis of a Class IC Antiarrhythmic, Pilsicainide, in Patients with Cardiac Arrhythmias2006

    • Author(s)
      Ogawa, R, Kishi, R, Mihara, K, Takahashi, H, Takagi, A, Matsumoto, N, Masuhara, K, Nakazawa, K, Miyake, F, Kobayashi, S, Echizen, H.
    • Journal Title

      J Clin Pharmaol 46

      Pages: 59-68

    • Related Report
      2008 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] Different contributions of polymorphisms in VKORC1 and CYP2C9 to intra- and inter-population differences in maintenance dose of warfarin in Japanese, Caucasians and African Americans2006

    • Author(s)
      Takahashi, H, Wilkinson, GR, Nutescu, EA, Morita, T, Ritchie, M, Scordo, MG, Pengo, V, Barban, M, Padrini, R, Ieiri I, Otsubo, K, Kashima T, Kimura S, Kijima S, Echizen H
    • Journal Title

      Pharmacogenetics & Genomics 16

      Pages: 101-110

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Population Pharmacokinetic and Pharmacodynamic Analysis of a Class IC Antiarrhythmic, Pilsicainide, in Patients with Cardiac Arrhythmias.2006

    • Author(s)
      Ogawa, R, Kishi, R, Mihara, K, Takahashi, H, Takaga, A, Matsumoto, N, Masuhara, K, Nakazawa, K, Miyake, F, Kobayashi, S, Echizen,H.
    • Journal Title

      J Clin Pharmaol 46

      Pages: 59-68

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 個別化されたワルファリン療法への道2006

    • Author(s)
      越前宏俊
    • Journal Title

      日本血栓止血学会誌 17

      Pages: 430-433

    • Related Report
      2006 Annual Research Report
  • [Journal Article] CYPの遺伝多型と抗不整脈薬2006

    • Author(s)
      越前宏俊
    • Journal Title

      Jpn J Electrocardiol 26

      Pages: 195-200

    • NAID

      10019171937

    • Related Report
      2006 Annual Research Report
  • [Presentation] 白癬患者に対するイトラコナゾールパルス療法施行時のCYP3A活性の経時的変化2009

    • Author(s)
      柴田壮一、高橋晴美、小野紀子、和田直子、久保博昭、篠崎公一、齋藤京、稲本伸子、越前宏俊、厚田幸一郎
    • Organizer
      日本臨床薬理学会第30回年会
    • Place of Presentation
      横浜
    • Related Report
      2009 Final Research Report
  • [Presentation] 内因性N^-メチルニコチンアミドおよびL^-カルニチンによる腎尿細管トランスポーター活性評価の試み2008

    • Author(s)
      小川竜一、越前宏俊
    • Organizer
      医療薬学フォーラム2008
    • Place of Presentation
      東京
    • Year and Date
      2008-07-10
    • Related Report
      2008 Self-evaluation Report
  • [Presentation] 内因性N^1-メチルニコチンアミドの腎クリアランスによる腎有機カチオントランスポーター活性の評価2007

    • Author(s)
      小川竜一、越前宏俊
    • Organizer
      第28回日本臨床薬理学会年会
    • Place of Presentation
      宇都宮
    • Year and Date
      2007-11-12
    • Related Report
      2008 Self-evaluation Report
  • [Presentation] Population differences in the contribution of genetic polymolphism of phamlacoki netics/phaarmacodynamics toward drug response2007

    • Author(s)
      Echizen H
    • Organizer
      4th World Conference on Drug Absorption, Transport and Delivery
    • Place of Presentation
      Kanazawa
    • Year and Date
      2007-06-21
    • Related Report
      2007 Annual Research Report
  • [Book] 医療薬物代謝学2010

    • Author(s)
      越前宏俊
    • Publisher
      医学評論社
    • Related Report
      2009 Final Research Report
  • [Book] 医療薬物代謝学2009

    • Author(s)
      越前宏俊(分担執筆)
    • Total Pages
      187
    • Publisher
      医学評論社
    • Related Report
      2009 Annual Research Report
  • [Book] 最新創薬学2007臨床薬物動態の実戦-トランスレーショナルPKIPD研究:ワルファリン2007

    • Author(s)
      高橋 晴美、越前 宏俊
    • Total Pages
      15
    • Publisher
      メディカルドゥ
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.my-pharm.ac.jp/~pharmaco/index.html

    • Related Report
      2008 Self-evaluation Report

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

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