Quantitative analysis of genetic factors affecting the extent of drug interactions via mechanism based inhibition of cytochrome P450

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590668
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Keio University
• Principal Investigator: OHTANI Hisakazu 慶應義塾大学, 薬学部, 教授 (70262029)
• Co-Investigator(Kenkyū-buntansha): YAMAMOTO Koujirou 群馬大学, 医学部, 教授 (70174787)
• Co-Investigator(Renkei-kenkyūsha): AKIYOSHI Takeshi 慶應義塾大学, 薬学部, 助教 (50399143) ; YAMAZAKI Hiroshi 昭和薬科大学, 薬学部, 教授 (30191274)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 薬物相互作用 / 個人差 / テーラーメード医療 / 不可逆的阻害 / 遺伝子多型

Outline of Final Research Achievements

There seems to be considerable inter-individual variations in the extent of drug interactions, especially via the inhibition of oxidative metabolic enzymes, P450s. This study aimed to investigate quantitatively the influence of genetic variation of P450s, such as CYP3A4 and CYP2D6, on the extent of drug interaction in the in vitro studies using genetic variants. As a result of enzymatic study with probe substrates and mechanism-based inhibitors (MBI), we concluded that the inhibitory potencies of MBI differ among genetic variants. These results suggest that the genetic variation of metabolic enzymes affect the extent of drug interactions caused by their inhibitors, as well as the pharmacokinetics of their substrate drugs.

Free Research Field

臨床薬物動態学、医薬品情報学、薬物治療の情報科学