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2014 Fiscal Year Final Research Report

Quantitative prediction of the bioavailability of drugs based on the activities of dexofication enzymes/transporters

Research Project

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Project/Area Number 24689009
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypePartial Multi-year Fund
Research Field Medical pharmacy
Research InstitutionThe University of Tokyo

Principal Investigator

MAEDA Kazuya  東京大学, 薬学研究科(研究院), 講師 (00345258)

Project Period (FY) 2012-04-01 – 2015-03-31
Keywordsバイオアベイラビリティ / 消化管吸収 / 肝初回通過 / トランスポーター / 数理モデル
Outline of Final Research Achievements

The purpose of this study is to identify the novel molecular mechanisms dominating the bioavailability (BA), which is defined as the fraction of orally-administered dose reached to the blood circulation, and quantitative prediction of BA by utilizing in vitro experimental data and mathematical model. Regarding the small intestine, I succeeded the quantitative estimation of decreased function of BCRP by genetic polymorphism (c.421C>A) by describing the relationship between the function of mutated BCRP and FaFg values of BCRP substrate drugs. I constructed the mathematical model with considering the uneven distribution of P-gp and CYP3A4 along the small intestine and succeeded in the good prediction of FaFg of multiple CYP3A4/P-gp substrate drugs by setting appropriate scaling factors for relating the in vitro data to in vivo human clinical data.

Free Research Field

分子薬物動態学

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Published: 2016-06-03  

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