2010 Fiscal Year Final Research Report
Role of drug transporters in the anticancer drug-induced hematotoxicity
| Project/Area Number |
21790145
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Medical pharmacy
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
MAEDA Kazuya The University of Tokyo, 大学院・薬学系研究科, 助教 (00345258)
|
|---|
| Project Period (FY) |
2009 – 2010
|
| Keywords | 血液毒性 / トランスポーター / 好中球 / 抗がん剤 / 体内動態 / OATP1B3 / MRP2 |
|---|
| Research Abstract |
Based on the recent report demonstrating the relationship between genetic polymorphisms of OATP1B3 and MRP2 and risk of neutropenia induced by docetaxel, I clarified this mechanisms by in vitro experiments. I showed that docetaxel was taken up into human hepatocytes mainly by OATP1B3 and that the decreased function of MRP2 in hematopoietic cells or their precursor cells lead to the increased risk of hematotoxicity. I also constructed a mathematical model describing pharmacokinetics of docetaxel and subsequent effect on the decrease of hematopoietic cells and quantitatively evaluated the impact of OATP1B3 and MRP2 functions on the risk of docetaxel-induced hematotoxicity.
|
