Quantitative prediction of the bioavailability of drugs based on the activities of dexofication enzymes/transporters
| Project/Area Number |
24689009
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Partial Multi-year Fund |
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| Research Field |
Medical pharmacy
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MAEDA Kazuya 東京大学, 薬学研究科(研究院), 講師 (00345258)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| 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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| 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 |
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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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Report
(4 results)
Research Products
(35 results)
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[Journal Article] Mechanisms of pharmacokinetic enhancement between ritonavir and saquinavir; micro/small dosing tests using midazolam (CYP3A4), fexofenadine (p-glycoprotein), and pravastatin (OATP1B1) as probe drugs.2013
Author(s)
Ieiri I, Tsunemitsu S, Maeda K, Ando Y, Izumi N, Kimura M, Yamane N, Okuzono T, Morishita M, Kotani N, Kanda E, Deguchi M, Matsuguma K, Matsuki S, Hirota T, Irie S, Kusuhara H, Sugiyama Y.
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Journal Title
J Clin Pharmacol, 1-16
Volume: 53
Issue: 6
Pages: 1-16
DOI
Related Report
Peer Reviewed
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