Influence of body mass index change on pharmacokinetics in clinical practice

• Project/Area Number: 24790149
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Kanazawa University
• Principal Investigator: SAWAMOTO Kazuki 金沢大学, 大学病院, 助教 (80608696)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: BMI / 肥満 / タクロリムス / シクロスポリン / 薬物動態変動 / 個別化医療 / 投与設計 / バイオアベイラビリティー / 免疫抑制剤 / フェンタニル / 個人間変動 / トランスポーター

Outline of Final Research Achievements

We found that the dose-normalized steady-state trough concentration ratio of orally administered tacrolimus in blood is increased in obese patients with a body mass index (BMI) over 25 compared with other patients having normal and lower BMI. In order to clarify the mechanisms involved in this increase, we examined the influence of obesity on tacrolimus pharmacokinetics using genetically obese model rats. Rats (18 weeks of age) were given tacrolimus intravenously or orally. The blood concentrations of this drug in obese rats were higher than those in lean rats after administration via both routes. The bioavailability of tacrolimus was significantly increased in obese rats compared with lean rats. Protein expression of P-glycoprotein in the small intestine was significantly decreased in obese rats. These results indicate that the high blood concentration of tacrolimus in obese patients is presumably a consequence of increased tacrolimus bioavailability.

Research Products

• [Journal Article] Mechanisms of Lower Maintenance Dose of Tacrolimus in Obese Patients (2014)
  • Author(s): Sawamoto K, Huong TT, Sugimoto N, Mizutani Y, Sai Y, Miyamoto KI.
  • Journal Title: Drug Metabolism and Pharmacokinetics Volume: 29 Issue: 4 Pages: 341-347
  • DOI: 10.2133/dmpk.DMPK-13-RG-110
  • NAID: 130004463396
  • ISSN: 1347-4367, 1880-0920
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mechanisms of lower maintenance dose of tacrolimus in obese patients (2014)
  • Author(s): Kazuki Sawamoto, Tran T Huong, Natsumi Sugimoto, Yuka Mizutani, Yoshimichi Sai, Ken-ichi Miyamoto
  • Journal Title: Drug Metabolism and Pharmacokinetics Volume: 印刷中
  • NAID: 130004463396
  • Peer Reviewed
• [Presentation] ラット肥満モデルにおけるタクロリムスのバイオアベイラビリティー上昇 (2014)
  • Author(s): 澤本一樹、Tran Huong、杉本奈津美、水谷友香、宮本謙一、崔 吉道
  • Organizer: 第29年会日本薬剤学会
  • Place of Presentation: 大宮ソニックシティビル (埼玉)
  • Year and Date: 2014-05-20 – 2014-05-22
• [Presentation] ラット肥満モデルにおけるタクロリムスのバイオアベイラビリティー上昇 (2014)
  • Author(s): 澤本一樹、Tran Huong、杉本奈津美、水谷友香、宮本謙一、崔 吉道
  • Organizer: 日本薬剤学会第29年会
  • Place of Presentation: 大宮ソニックシティビル (埼玉)
• [Presentation] 肥満状態におけるタクロリムス体内動態変動の解明 (2013)
  • Author(s): 澤本一樹、Tran Huong、水谷友香、杉本奈津美、崔 吉道、宮本謙一
  • Organizer: 第8回トランスポーター研究会
  • Place of Presentation: 熊本大学 薬学部 (熊本)
• [Presentation] BMI値の変動にともなうシクロスポリン及びタクロリムスの血中濃度変化 (2012)
  • Author(s): 澤本一樹、杉本奈津美、Tran Huong、崔 吉道、宮本謙一
  • Organizer: 医療薬学フォーラム
  • Place of Presentation: 福岡国際会議場（福岡県）
• [Remarks] 金沢大学附属病院薬剤部 業績
  • URL: http://web.hosp.kanazawa-u.ac.jp/bu/yaku/
• [Remarks] 金沢大学附属病院薬剤部最新情報
  • URL: http://web.hosp.kanazawa-u.ac.jp/bu/yaku/index.html