| Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2013: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2012: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2011: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Research Abstract |
Cytochrome P450s (CYPs) play a key role in human drug metabolism, and five CYP isoforms can metabolize more than 90% of clinical drugs in the market. In this study, we focused on a chain reaction of drug metabolism played by five isoforms. Although an anti-depressant amitriptyline is mainly metabolized by CYP1A2, 2C19, and 2D6, its metabolite nortriptyline, which is structurally similar to amitriptyline, was found to be poorly metabolized by these isoforms. On the other hand, CYP2C9 is a poor metabolizer of amitriptyline although it is homologous with 2C19 in amino acid sequence and three dimensional structure. We revealed that the drug specificity is regulated by the basicity of an amino acid residue at position 72.
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