Establishment of therapeutic strategy for cancer treatment in special population using pharmacokinetic-pharmacodynamic (PK-PD) model

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K14963
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: Kobuchi Shinji 京都薬科大学, 薬学部, 助教 (70747237)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 個別化医療 / 特定患者集団 / 薬物動態―薬力学的（PK-PD）モデル解析 / 母集団薬物動態解析 / 腎機能障害 / ファーマコメトリクス

Outline of Final Research Achievements

In cancer chemotherapy, it is difficult to adjust the dosage for patients with impaired of organ function or complications. To maximize antitumor effects and minimize toxicities, evidence-based dose setting method for each patient is required. In the current study, pharmacokinetic (PK) and pharmacodynamic/toxicodynamic (PD) studies of 5-fluorouracil (5-FU)-related agents and oxaliplatin were performed using rats to clarify the factors that influence on the PK and PD. We successfully developed the PK-PD model that can describe the time-course alterations of drug concentrations in plasma, tumor volume, and onset and degree of toxicities. These models would contribute to the personalization and optimal dosage regimen of 5-FU, capecitabine, and oxaliplatin for the treatment of colorectal cancer.

Free Research Field

薬物動態学

Academic Significance and Societal Importance of the Research Achievements

がん化学療法の個別化医療実現に向け、抗がん剤の血中濃度に基づく投与量調節法の研究、開発は世界中で展開されている。しかし、高齢化が急速に進む本邦においては、血漿中濃度だけでなく、合併症や臓器機能も考慮した投与設計が必要であるが、多様な患者背景を解析するには課題が多く、基礎的情報も少ない。本研究では、抗がん剤治療成績の個体間変動因子を明らかにし、それらを定量的に記述可能な数理学的モデルを開発した。これらの成果はスペシャルポピュレーションへの最適な投与設計法の確立に向けて貢献できるものと考えられ、抗がん剤の治療成績向上が期待される。