2009 Fiscal Year Final Research Report
Prediction of drug distribution into the brain by the model with intrinsic transporter activity
| Project/Area Number |
19390038
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
OHTSUKI Sumio Tohoku University, 大学院・薬学研究科, 准教授 (60323036)
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| Co-Investigator(Renkei-kenkyūsha) |
KAMIIE Junichi 麻布大学, 獣医学部, 講師 (10400269)
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| Project Period (FY) |
2007 – 2009
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| Keywords | 脳関門 / P-糖タンパク質 / LC-MS / MS / 単分子活性 / トランスポーター / 脳分布 / 血管内皮細胞 / 培養細胞 |
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| Research Abstract |
Te purpose of this study was to predict drug distribution into the brain based on the model with intrinsic transport activity and absolute expression amount of transporters. At first, we established the quantification method of mouse mdr1a by means of LC-MS/MS with in slico target tryptic peptide selection. Using the established method, the absolute expression amounts of mdr1a were determined in mouse brain capillaries and mdr1a-expressing cultured cells. The transport activity of mdr1a was examined by transcellular transport study. The Kp, brain ratio and Kp,brain of each drug were calculated based on the model integrating absolute expression amounts and transport activity, and these predicted values were well-matched with the valued determined in vivo. The present results indicate that the established prediction model should be rational strategy to predict drug distribution into human brain.
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