| Budget Amount *help |
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2009: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2008: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2007: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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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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