Variability of bioavailability and intestinal absorption mechanism of mizoribine and bisoprolol

• Project/Area Number: 24590181
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: University of Toyama
• Principal Investigator: HASHIMOTO Yukiya 富山大学, 大学院医学薬学研究部(薬学), 教授 (90228429)
• Co-Investigator(Kenkyū-buntansha): NOZAWA Takashi 富山大学, 大学院医学薬学研究部(医学), 准教授 (00180737) ; ISHIDA Kazuya 富山大学, 大学院医学薬学研究部(薬学), 助教 (90550509)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: バイオアベイラビリオティ / ミゾリビン / 腎排泄性薬剤 / 消化管吸収機構 / トランスポーター

Outline of Final Research Achievements

The large variability of bioavailability (F) of drugs induces the positive correlation between oral clearance (CL/F) and apparent volume of distribution (V/F). In the present study, we performed the clinical pharmacokinetic trials of mizoribine and bisoprolol. The population pharmacokinetic analysis was performed by use of the nonlinear mixed effects model (NONMEM) program. As the results, we observed the positive correlation between CL/F and V/F of mizoribine in pediatric patients of renal transplantation, indicating large variability of F of the drug. In addition, we observed the positive correlation between CL/F and V/F of bisoprolol in Japanese patients with cardiovascular diseases, indicating large variability of F of the drug.

Research Products

• [Journal Article] Advantages and disadvantages of conditional estimation methods for population pharmacokinetic analysis of mizoribin. (2014)
  • Author(s): Kazuya Ishida, Miki Fukao, Hiromichi Ith, Osamu Uemura, and Yukiya Hashimoto
  • Journal Title: Jpn. J. Health Care Sci. Volume: 40 Pages: 643-651
  • NAID: 130005108788
  • Peer Reviewed
• [Journal Article] Variability of Bioavailability and Intestinal Absorption Characteristics of Bisoprolol (2013)
  • Author(s): Kazuya Ishida
  • Journal Title: Drug Metabolism and Pharmacokinetics Volume: 28 Issue: 6 Pages: 491-496
  • DOI: 10.2133/dmpk.DMPK-13-RG-017
  • NAID: 130004463332
  • ISSN: 1347-4367, 1880-0920
  • Peer Reviewed
• [Journal Article] Effect of Salt Intake on Bioavailability of Mizoribine in Healthy Japanese Males (2013)
  • Author(s): Ishida K, Fukao M, Watanabe H, Taguchi M, Miyawaki T, Matsukura H, Uemura O, Zhang Z, Unadkat JD, Hashimoto Y
  • Journal Title: Drug Metabolism and Pharmacokinetics Volume: 28 Issue: 1 Pages: 75-80
  • DOI: 10.2133/dmpk.DMPK-12-NT-043
  • NAID: 130004463290
  • ISSN: 1347-4367, 1880-0920
  • Peer Reviewed
• [Presentation] 小腸H+／三級アミン対向輸送系の活性における基質の脂溶性および極性表面積重要性 (2015)
  • Author(s): 深尾美紀、石田和也、松葉映美、渡邉柚梨、堀江明日佳、橋本征也
  • Organizer: 日本薬学会第１３５年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] Variability of bioavailability and intestinal absorption machanisms of metoprolol (2013)
  • Author(s): Miki Fukao
  • Organizer: 日本薬物動態学会第28回年会
  • Place of Presentation: タワーホール船堀（東京都）
• [Presentation] Variability of bioavailability of mizoribine in healthy males and mechanisms of barrier function for intestinal absorption (2013)
  • Author(s): Kazuya Ishida
  • Organizer: 日本薬物動態学会第28回年会
  • Place of Presentation: タワーホール船堀（東京都）
• [Presentation] Variability of bioavailability and intestinal absorption characteristics of bisoprolol (2013)
  • Author(s): Kazuya Ishida
  • Organizer: 第7回次世代を担う若手医療薬科学シンポジウム
  • Place of Presentation: 東北大学片平キャンパス さくらホール(宮城県）
• [Presentation] ビソプロロールの消化管吸収特性とバイオアベイラビリティ変動性評価 (2013)
  • Author(s): 堀江 明日佳
  • Organizer: 日本薬学会第133年回
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] Effect of salt intake on bioavailability of mizoribine in healthy Japanese males (2012)
  • Author(s): Kazuya Ishida
  • Organizer: 18th North American ISSX meeting
  • Place of Presentation: Hilton Anatole Dallas Hotel, Dallas, Texas, USA
• [Presentation] ビソプロロールの消化管吸収機構と変動性評価 (2012)
  • Author(s): 堀江 明日佳
  • Organizer: 日本薬剤学会第27年会
  • Place of Presentation: 神戸国際会議場（兵庫県）
• [Presentation] Improvement of the intestinal absorption of mizoribine by salt intake in healthy Japanese males (2012)
  • Author(s): Miki Fukao
  • Organizer: 日本薬物動態学会第27回年会
  • Place of Presentation: タワーホール舟堀（東京都）