Novel monitoring system of fluoropyrimidines for personalized therapy based on PK/PD modeling using dihydropyrimidine dehydrogenase activity as a biomarker of predicting efficacy and side-effects.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590223
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: ITO Yukako 京都薬科大学, 薬学部, 講師 (30278444)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 薬物動態 / 抗がん剤 / PK/PD / DDS

Outline of Final Research Achievements

For personalized chemotherapy in colorectal cancer (CRC), the relationship between plasma ratio of dihydrouracil (UH2)/uracil (Ura) and pharmacokinetics parameters of 5-FU was investigated to evaluate the usefulness as a surrogate marker of DPD activity in liver. Based on the pharmacokinetic parameters estimated from CRC rats, we developed a pharmacokinetic-pharmacodynamic (PK-PD) model with plasma UH2/Ura ratio for predicting the tumor growth in CRC rats. Before 5-FU treatment, the measurement of UH2/Ura values as a surrogate biomarker of DPD activity in liver could predict tumor growth in CRC rats. Besides, the UH2/Ura ratio in plasma could be useful for the optimized dosage regimen for CRC chemotherapy. These findings would be cost-effective and helpful for personalized anti-cancer treatment

Free Research Field

薬物動態