| Budget Amount *help |
¥21,320,000 (Direct Cost: ¥16,400,000、Indirect Cost: ¥4,920,000)
Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2012: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
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| 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.
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