Kinetics of drug-induced dysglycemia

• Project/Area Number: 24590180
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: YASUHARA Masato 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (00127151)
• Co-Investigator(Kenkyū-buntansha): NAGATA Masashi 東京医科歯科大学, 医学部附属病院, 准教授 (40412829)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: dysglycemia / hyperglycemia / pentamidine / moxifloxacin / olanzapine / pharmacodynamics / pharmacokinetics / 血糖値上昇 / オランザピン / ニューキノロン系抗菌薬 / モキシフロキサシン / ペンタミジン / シメチジン / 薬物間相互作用

Outline of Final Research Achievements

Drug induced hyperglycemia　and　hypoglycemia　are　serious　side　effects　of　drugs.　We　have　investigated　the mechanisms of drug induced dysglycemia and the relationship between drug concentrations and changes in serum glucose in rats.
Pentamidine induced a dose dependent increase in serum glucose concentrations after intravenous infusion in rats and a significant　correlation　was　found　between　changes　in　serum　glucose　concentrations　and　serum pentamidine 　concentrations. Moxifloxacin induced histamine release dose-dependently, leading to an increase in serum epinephrine concentrations and hyperglycemia. A single intravenous dose of olanzapine caused a rise in serum glucose concentrations in a dose dependent manner. It was suggested that epinephrine is involved in the process of olanzapine-induced acute hyperglycemia.

Research Products

• [Journal Article] Pharmacokinetic–Pharmacodynamic Analysis of Sunitinib-Induced Thrombocytopenia in Japanese Patients with Renal Cell Carcinoma (2015)
  • Author(s): M. Nagata, Y. Ishiwata, Y. Takahashi, H. Takahashi, K. Saito, Y. Fujii, K. Kihara, M. Yasuhara
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 38 Issue: 3 Pages: 402-410
  • DOI: 10.1248/bpb.b14-00636
  • NAID: 130004872283
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Effects of Moxifloxacin on Serum Glucose Concentrations in Rats (2013)
  • Author(s): Y. Ishiwata, Y. Takahashi, M. Nagata, M. Yasuhara
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 36 Issue: 4 Pages: 686-690
  • DOI: 10.1248/bpb.b12-00930
  • NAID: 130003361398
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed
• [Journal Article] Effect of cimetidine on pentamidine induced hyperglycemia in rats (2012)
  • Author(s): T. Arino, S. Karakawa, Y. Ishiwata, M. Nagata, M. Yasuhara
  • Journal Title: Eur. J Pharmacol. Volume: 693 Issue: 1-3 Pages: 72
  • DOI: 10.1016/j.ejphar.2012.07.043
  • Peer Reviewed
• [Presentation] ラットにおけるオランザピン単回投与による血糖値上昇のメカニズム (2015)
  • Author(s): 中島 真由美、石渡 泰芳、永田 将司、高橋 弘充、根岸 健一、安原 眞人
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸学院大学
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] PK-PD理論を基盤とした副作用発現の機構解明とリスクファクターの探索 (2014)
  • Author(s): 永田将司
  • Organizer: 第24回日本医療薬学会年会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2014-09-27 – 2014-09-28
  • Invited
• [Presentation] 難病治療への挑戦 (2014)
  • Author(s): 安原眞人
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本（ホテル日航熊本）
• [Presentation] 薬物による中枢毒性評価のための薬力学的アプローチ (2013)
  • Author(s): 永田将司
  • Organizer: 日本薬剤学会第28年会
  • Place of Presentation: 名古屋(ウインクあいち）
• [Presentation] 薬物動態と薬理効果の速度論的研究 (2012)
  • Author(s): 安原眞人
  • Organizer: 日本薬剤学会第27年会
  • Place of Presentation: 神戸国際会議場
  • Invited
• [Remarks] 東京医科歯科大学医学部附属病院薬剤部ホームページ
  • URL: http://www.tmd.ac.jp/medhospital/medicine/framepage1.html
• [Remarks] 東京医科歯科大学医学部附属病院薬剤部ホームページ
  • URL: http://www.tmd.ac.jp/medhospital/medicine/framepage1.html