Role of drug transporters in the anticancer drug-induced hematotoxicity

点击翻译按钮获取中文摘要

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.