An attempt to develop a clinical test assessing hepatic CYP activity by urinary LC-MS assay of endogenous steroid metabolites

2008 Fiscal Year Self-evaluation Report

• Project/Area Number: 18590542
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Meiji Pharmaceutical University
• Principal Investigator: ECHIZEN Hirotoshi Meiji Pharmaceutical University, 薬学部, 教授 (00191924)
• Project Period (FY): 2006 – 2009
• Keywords: 薬物代謝 / LC-MS / ステロイド

Research Abstract

近年、薬物代謝酵素のゲノム解析が精力的になされ多くのSNPの存在が明らかとなったが、同時にゲノム情報の差異だけでは説明できない活性の個人差も明らかとなり、その原因については代謝酵素の基礎発現量に関わる環境あるいは発現調節機構の遺伝変異の存在が注目されているが, 未だにその本体は不明である, このため、再び個別患者における代謝活性表現型評価法の必要性が注目されている。従来から, 内因性コルチゾールの6β位水酸化反応がCYP3A4分子種により行われることに注目し、コルチゾールから6β水酸化への部分代謝クリアランスを評価する方法が検討されているが, 本研究では、この方法を他の内因性ステロイドホルモンの部位特異的な代謝物の測定に外挿しCYP3A4意外のCYP分子種の活性の個人差を評価する方法の開発を目的としている.

Research Products

• [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
  • Peer Reviewed
• [Journal Article] Reduced vancomycin clearance despite unchanged creatinine clearance in patients treated with vancomycin for longer than 4 weeks (2008)
  • Author(s): Nakayama H, Echizen H, Tanaka M, Sato M, Orii T
  • Journal Title: Ther Drug Monit 30 Pages: 103-107
  • Peer Reviewed
• [Journal Article] Bioequivalence studies between 0.5, 1, and 5 mg warfarin potassium tablets of new formula and those of standard formula (2008)
  • Author(s): Dochiguchi Y, Shiba S, Masuda Y, Kurihara Y, Hasegawa S, Echizen H
  • Journal Title: Jpn Pharmacol Ther 36 Pages: 401-409
  • Peer Reviewed
• [Journal Article] Proteomic & Transcriptomic Analyses of Retinal Pigment Epithelial Cells Exposed t-o REF-1/TFPI-2, a Growth Promoting Factor (2007)
  • 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
  • Peer Reviewed
• [Journal Article] A meta-analysis on the risk of developing malignancy associated with use of immunosuppressive agents in patients with inflammatory bowel disease (2007)
  • Author(s): Masunaga Y, Ohno K, Ogawa R, Hashiguchi M, Echizen H, Ogata H
  • Journal Title: Ann Pharmacother 41 Pages: 21-28
  • Peer Reviewed
• [Journal Article] Effect of low-dose macrolide antibiotics on theophylline disposition in pediatric patients (2007)
  • 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
  • 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 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 &amp ; Genomics 16 Pages: 101-110
  • Peer Reviewed
• [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, Takagi, A, Matsumoto, N, Masuhara, K, Nakazawa, K, Miyake, F, Kobayashi, S, Echizen, H.
  • Journal Title: J Clin Pharmaol 46 Pages: 59-68
  • Peer Reviewed
• [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
• [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
• [Remarks]
  • URL: http://www.my-pharm.ac.jp/~pharmaco/index.html