Development of support system for dosage adjustment to avoid drug-drug interactions caused by fluoropyrimidine anti-cancer drugs

Research Project

Project/Area Number	24390038
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Partial Multi-year Fund
Section	一般
Research Field	Medical pharmacy
Research Institution	The University of Tokyo
Principal Investigator	SAWADA Yasufumi 東京大学, 大学院薬学系研究科, 教授 (80114502)
Co-Investigator(Kenkyū-buntansha)	HORI Satoko 東京大学, 大学院情報学環, 准教授 (70313145) SATOH Hiroki 東京大学, 大学院薬学系研究科, 助教 (80451855)
Project Period (FY)	2012-04-01 – 2015-03-31
Project Status	Completed (Fiscal Year 2014)
Budget Amount *help	¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000) Fiscal Year 2014: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000) Fiscal Year 2013: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000) Fiscal Year 2012: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Keywords	薬物間相互作用 / フッ化ピリミジン系抗癌薬 / 薬物代謝酵素 / フェニトイン / ワルファリン / 薬物相互作用
Outline of Final Research Achievements	Fluoropyrimidine anti-cancer drugs cause the drug-drug interactions with anti-epileptic drugs (phenytoin) and anticoagulants (warfarin). In this study, we conducted experiment using HepaRG cells, and then elucidated the mechanism of this interaction. Also, we collected cases which were co-administrated fluoropyrimidine anti-cancer drugs and phenytoin or warfarin, and constructed pharmacokinetic-pharmacodynamic model that can represent the interaction. When used in combination with fluoropyrimidine anti-cancer drugs, it is possible to predict a phenytoin dosage as not to vary the phenytoin concentration using the constructed models.