Investigation of transport mechanisms of lipid and lipophilic drugs

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15155
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: TAKADA Tappei 東京大学, 医学部附属病院, 講師 (90376468)
• Co-Investigator(Kenkyū-buntansha): 豊田 優 東京大学, 医学部附属病院, 特任研究員 (80650340)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 脂質 / 生理学 / 薬理学 / 薬物動態学 / トランスポーター

Outline of Final Research Achievements

Only free drugs have been believed to be carried into tissues through active or passive transport. However, considering that lipoproteins function as carriers of serum lipids, we hypothesized that lipoproteins can associate with certain drugs and mediate their transport into tissues in lipid-associated form. By a series of in vitro and in vivo studies, we showed the association of various drugs with lipoproteins and the uptake of lipoprotein-associated drugs through a lipoprotein receptor-mediated process. In clinical studies, investigation of the effect of lipoprotein apheresis on serum drug concentrations in patients with familial hypercholesterolemia demonstrated that lipoprotein-mediated drug transport occurs in humans as well as in mice. These findings represent a new concept regarding the transport and metabolism of drugs in the body and suggest that the role of lipoprotein-mediated drug transport should be considered when developing effective and safe pharmacotherapies.

Free Research Field

医療系薬学