Significant factors associated with the decrease in CYP3A activity in patients with chronic renal failure

• Project/Area Number: 15K18926
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Oita University
• Principal Investigator: Suzuki Yosuke 大分大学, 医学部, 薬物動態解析室主任 (10737191)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: CYP3A / 慢性腎不全 / Phenoconversion / 3-indoxyl sulfate / CYP3A5 / 腎移植 / 代謝 / 薬物動態

Outline of Final Research Achievements

The aim of this study was to identify significant factors associated with the decrease in CYP3A activity in patients with chronic renal failure. Compared with before kidney transplantation, plasma 4β-hydroxycholesterol concentrations were significantly elevated on days 90 and 180 after living kidney transplantation. Plasma concentrations of 4β-hydroxycholesterol on days 90 and 180 after kidney transplantation were significantly higher in the presence of the CYP3A5*1 allele than in the absence of the CYP3A5*1 allele. Furthermore, accumulation of indoxyl sulfate was associated with phenoconversion of CYP3A in stable kidney transplant recipients.

Research Products

• [Journal Article] CYP3A5 polymorphism affects the increase in CYP3A activity after living kidney transplantation in patients with end stage renal disease. (2015)
  • Author(s): Suzuki Y, Fujioka T, Sato F, Matsumoto K, Muraya N, Tanaka R, Sato Y, Ohno K, Mimata H, Kishino S, Itoh H.
  • Journal Title: Br J Clin Pharmacol Volume: 80(6) Issue: 6 Pages: 1421-1428
  • DOI: 10.1111/bcp.12733
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Phenoconversion of CYP3A in chronic renal failure; what is the factor involved? (2017)
  • Author(s): Suzuki Y, Muraya N, Fujioka T, Sato F, Tanaka R, Matsumoto K, Sato Y, Ohno K, Mimata H, Kishino S, Itoh H
  • Organizer: 15th International Congress of Therapeutic Drug Monitoring & Clinical Toxicology
  • Place of Presentation: Kyoto International Conference Center, Kyoto, Japan
  • Year and Date: 2017-09-24
  • Int'l Joint Research
• [Presentation] 腎機能障害時におけるCYP3AのPhenoconversionに関連する因子の探索 (2015)
  • Author(s): 村谷菜々子、鈴木陽介、藤岡孝志、佐藤文憲、松本邦洋、田中遼大、佐藤雄己、大野恵子、三股浩光、岸野吏志、伊東弘樹
  • Organizer: 第36回日本臨床薬理学会学術総会
  • Place of Presentation: 京王プラザホテル新宿（東京都新宿区）
  • Year and Date: 2015-12-09
• [Presentation] CYP3A5遺伝子多型およびインドキシル硫酸の蓄積が生体腎移植後のCYP3A活性の回復に与える影響 (2015)
  • Author(s): 村谷菜々子、鈴木陽介、藤岡孝志、佐藤文憲、松本邦洋、田中遼大、佐藤雄己、大野恵子、三股浩光、岸野吏志、伊東弘樹
  • Organizer: 第25回日本医療薬学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-11-21
• [Presentation] CYP3A5 polymorphism and accumulation of indoxyl sulfate affect the rate of increase in CYP3A activity after living kidney transplantation in patients with end stage renal disease. (2015)
  • Author(s): Suzuki Y, Fujioka T, Muraya N, Sato F, Matsumoto K, Tanaka R, Sato Y, Ohno K, Mimata H, Kishino S, Itoh H.
  • Organizer: 14th International Congress of Therapeutic Drug Monitoring & Clinical Toxicology
  • Place of Presentation: Congress Centre De Doelen, Rotterdam, The Netherlands
  • Year and Date: 2015-10-11
  • Int'l Joint Research
• [Presentation] CYP3A5 Polymorphism Affects the Increase in CYP3A Activity after Living Kidney Transplantation in Patients with End Stage Renal Disease. (2015)
  • Author(s): Suzuki Y, Fujioka T, Sato F, Matsumoto K, Muraya N, Tanaka R, Sato Y, Ohno K, Mimata H, Kishino S, Itoh H.
  • Organizer: The 12th Congress of the European Association for Clinical Pharmacology and Therapeutics
  • Place of Presentation: Melia Castilla Hotel, Madrid, Spain
  • Year and Date: 2015-06-27
  • Int'l Joint Research