Mechanisms of the pharmacokinetic variability and optimization of drug therapy in children with congenital heart disease

• Project/Area Number: 15K08091
• 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: Taguchi Masato 富山大学, 大学院医学薬学研究部(薬学), 准教授 (20324056)
• Co-Investigator(Kenkyū-buntansha): 市田 蕗子 富山大学, 事務局, 学長補佐 (30223100) ; 廣野 恵一 富山大学, 附属病院, 助教 (80456384)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ワルファリン / タダラフィル / 先天性心疾患 / 薬物体内動態 / 小児 / 蛋白漏出性胃腸症 / シルデナフィル / Ｐ-糖タンパク質 / 小児薬物動態

Outline of Final Research Achievements

There has been a limited number of reports documenting the pharmacokinetics of drugs in children with congenital heart disease. We demonstrated that the SIZE parameter appeared to be an effective way to describe the pediatric dose response relationship of warfarin, and that the anti coagulant effect of the drug was changed by the VKORC1 genotype and concomitant use of bosentan. We also found that the unbound fraction of tadalafil was tend to increase in the patients with protein-losing enteropathy. These efforts could provide an important basis for the proper use of drugs in children with heart disease.

Research Products

• [Journal Article] The possible clinical impact of risperidone on P-glycoprotein-mediated transport of tacrolimus: A case report and in vitro study. (2018)
  • Author(s): Watanabe N, Higashi H, Nakamura S, Nomura K, Adachi Y, Taguchi M.
  • Journal Title: Biopharm Drug Dispos Volume: 39 Issue: 1 Pages: 30-37
  • DOI: 10.1002/bdd.2109
  • Peer Reviewed
• [Journal Article] <i>In Vitro</i> P-Glycoprotein-Mediated Transport of Tadalafil: A Comparison with Sildenafil (2017)
  • Author(s): Higashi H, Watanabe N, Tamura R, Taguchi M.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 40 Issue: 8 Pages: 1314-1319
  • DOI: 10.1248/bpb.b17-00278
  • NAID: 130005876268
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed
• [Journal Article] <i>In Vitro</i> Enhancement of Carvedilol Glucuronidation by Amiodarone-Mediated Altered Protein Binding in Incubation Mixture of Human Liver Microsomes with Bovine Serum Albumin (2016)
  • Author(s): Makoto Sekimoto, Tohru Takamori, Saki Nakamura, Masato Taguchi
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 39 Issue: 8 Pages: 1359-1363
  • DOI: 10.1248/bpb.b16-00360
  • NAID: 130005254702
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A model analysis for dose-response relationship of warfarin inJapanese children: An introduction of the SIZE parameter (2016)
  • Author(s): Nakamura S, Watanabe N, Yoshimura N, Ozawa S, Hirono K, Ichida F, and Taguchi M.
  • Journal Title: Drug Metababolism and Pharmacokinetics Volume: 31 Issue: 3 Pages: 234-241
  • DOI: 10.1016/j.dmpk.2016.03.007
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] P-gp発現細胞株におけるタダラフィルの経細胞輸送～シルデナフィルとの比較 (2017)
  • Author(s): 東宏伎、渡辺直、田村理香、田口雅登
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-24
• [Presentation] 蛋白漏出性胃腸症患者におけるタダラフィルの血漿蛋白結合率変動 (2017)
  • Author(s): 髙森 徹、重冨七海、神谷健太、青木正哉、芳村直樹、小澤綾佳、斉藤和由、廣野恵一、市田蕗子、田口雅登
  • Organizer: 第34回日本TDM学会・学術総会
• [Presentation] タクロリムスの消化管吸収に及ぼすリスペリドンの影響 (2016)
  • Author(s): 4) 田口雅登，渡辺 直，東 宏伎，中村早稀，野村恵子，足立雄一
  • Organizer: 日本臨床薬理学会第136年会
  • Place of Presentation: 米子
  • Year and Date: 2016-12-01
• [Presentation] 肝ミクロソームを用いたカルベジロールのグルクロン酸抱合反応系に及ぼすアミオダロンの影響 (2016)
  • Author(s): 関本 真、高森 徹、勝眞愛梨沙、中村早稀、田口雅登
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-26
• [Presentation] P-糖タンパク質を介したタクロリムスの経細胞輸送に及ぼすリスペリドンの影響 (2016)
  • Author(s): 渡辺 直、東 宏伎、中村早稀、野村恵子、足立雄一、田口雅登
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-26
• [Presentation] 小児期におけるワルファリン抗凝固作用の共変量に関する長期データ解析 (2015)
  • Author(s): 田口雅登、中村早稀、渡辺 直、芳村直樹、小澤綾佳、廣野恵一、市田蕗子
  • Organizer: 第42回日本小児臨床薬理学会学術集会
  • Place of Presentation: 熊本
  • Year and Date: 2015-11-14