Identification of endogenous biomarkers to predict the altered activities of drug transporters by environmental factors

• Project/Area Number: 26460199
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Kyushu University
• Principal Investigator: Hirota Takeshi 九州大学, 薬学研究院, 准教授 (80423573)
• Co-Investigator(Kenkyū-buntansha): 家入 一郎 九州大学, 薬学研究院, 教授 (60253473)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 薬剤反応性 / 発現制御 / 薬物トランスポーター / バイオマーカー / クルクミン

Outline of Final Research Achievements

Curcumin, a commonly used spice, is a naturally occurring polyphenol. In this study, we assessed the influence of prior administration of curcumin on the pharmacokinetics of SASP. Orally 4 to 5 days’ time lag between SASP and curcumin intake disappeared the interaction. The disappeared interaction may be responsible for the extremely low bioavailability of curcumin and the disappearance of curcumin in the gastro-intestinal tracts before the administration of SASP. Our findings suggested that 4 to 5 days’ time lag is necessary to avoid the drug interaction between BCRP substrates and curcumin.
In addition to the effects of curcumin, we analyzed the correlation between exosomal miR-328 in plasma, which leaks from the intestines and BCRP activity in human. Exosomal miR-328 levels positively correlated (P < 0.05) with SASP AUC0-48, suggesting that exosomal miR-328 in plasma has potential as a possible biomarker for estimating BCRP function in the human intestines.

Research Products

• [Journal Article] Effect of Curcumin on Sulfasalazine Pharmacokinetics in Healthy Volunteers (2016)
  • Author(s): Tomoko Tokumoto, Takeshi Hirota, Keisuke Gotanda, Miyuki Kimura, Shin Irie, Masato Fukae and Ichiro Ieiri
  • Journal Title: Journal of Drug Metabolism & Toxicology Volume: 7 Pages: 1000206-1000206
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Circulating intestine-derived exosomal miR-328 in plasma, a possible biomarker for estimating BCRP function in the human intestines (2016)
  • Author(s): Gotanda K, Hirota T, Saito J, Fukae M, Egashira Y, Izumi N, Deguchi M, Kimura M, Matsuki S, Irie S, Ieiri I
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 32299-32299
  • DOI: 10.1038/srep32299
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Sulfasalazine disposition in subject with 376C>T (nonsense mutation) and 421C>A variants in ABCG2 gene. (2015)
  • Author(s): Gotanda K, Tokumoto T, Hirota T, Fukae M, Ieiri I.
  • Journal Title: Br J Clin Pharmacol Volume: 未定 Issue: 5 Pages: 1236-1237
  • DOI: 10.1111/bcp.12654
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] ABCG2遺伝子376C>T変異がスルファサラジンの体内動態に与える影響 (2016)
  • Author(s): 廣田豪、五反田圭介、徳本知子、深江真登、家入一郎
  • Organizer: 日本薬物動態学会 第31回年会
  • Place of Presentation: 長野県松本市
  • Year and Date: 2016-10-13
• [Presentation] Sulfasalazine disposition in subject with 376C>T (nonsense mutation) variant in ABCG2 gene (2016)
  • Author(s): Takeshi Hirota, Keisuke Gotanda, Tomoko Tokumoto, Masato Fukae and Ichiro Ieiri
  • Organizer: International Society for the Study of Xenobiotics
  • Place of Presentation: Busan, Korea
  • Year and Date: 2016-06-13
  • Int'l Joint Research
• [Presentation] クルクミンが消化管BCRP発現へ与える影響評価 (2015)
  • Author(s): 徳本 知子, 廣田 豪, 五反田 圭介, 深江 真登, 家入 一郎
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-26