Woodburn Kathryn W, Schatz Peter J, Fong Kei-Lai, Wilson Susan D, Ferrell Thomas, Spainhour Charles B, Norton Daniel
Affymax, Inc, Palo Alto, California 94304, USA.
Drug Chem Toxicol. 2008;31(2):229-44. doi: 10.1080/01480540701873186.
The pharmacology, toxicokinetics, and safety of Hematide, a synthetic peptidic erythropoiesis-stimulating agent (ESA), were characterized. Hematide was given intravenously (0, 0.5, 5, and 50 mg/kg) weekly for five weeks with a 6- (rat) and 12-week (monkey) recovery period. The pharmacological action of Hematide resulted in polycythemia. Histopathology consistent with drug-induced exaggerated pharmacology was observed primarily in rats. Secondary sequelae resulting from pronounced polycythemia was considered the cause of deaths in rats and a single high-dose monkey. Toxicokinetic analysis indicated prolonged exposure. In conclusion, Hematide is a potent ESA and the safety and efficacy profile support clinical development.
对一种合成肽类促红细胞生成素（ESA）药物Hematide的药理学、毒代动力学和安全性进行了表征。每周静脉注射Hematide（0、0.5、5和50mg/kg），持续五周，大鼠恢复期为6周，猴子为12周。Hematide的药理作用导致红细胞增多症。主要在大鼠中观察到与药物诱导的过度药理作用一致的组织病理学变化。明显的红细胞增多症导致的继发性后遗症被认为是大鼠和一只高剂量猴子死亡的原因。毒代动力学分析表明暴露时间延长。总之，Hematide是一种有效的ESA，其安全性和有效性支持临床开发。
