McMahon F G, Vargas R, Ryan M, Jain A K, Abels R I, Perry B, Smith I L
Clinical Research Center, New Orleans, LA 70112.
Blood. 1990 Nov 1;76(9):1718-22.
A double-blind, placebo-controlled study of the pharmacokinetics and safety of multiple doses of recombinant human erythropoietin [rHuEPO 150 or 300 U/kg either by intravenous (IV) bolus or subcutaneously (SC)] in normal male subjects demonstrated that rHuEPO had a dose-related effect on the hematocrit independent of the route of administration and that multiple doses of rHuEPO had no direct pressor effects. When rHuEPO was injected IV, a monoexponential decrease in serum EPO level was evident for 18 to 24 hours postdose. Absorption of SC injected rHuEPO occurred more slowly, with relatively low serum EPO levels being maintained for 48 hours. All rHuEPO antibody titer determinations were negative. With the exception of significant increases in hemoglobin and hematocrit, no clinically significant changes occurred. No hypertensive, convulsive, or thrombotic events were observed. Of the adverse experiences observed in 10 subjects, none was considered clinically significant, and none of the subjects dropped out because of adverse experiences.
一项针对正常男性受试者的双盲、安慰剂对照研究，旨在探讨多次剂量的重组人促红细胞生成素[rHuEPO，静脉推注（IV）或皮下注射（SC），剂量分别为150或300 U/kg]的药代动力学和安全性。结果表明，rHuEPO对血细胞比容有剂量相关效应，且与给药途径无关，多次剂量的rHuEPO无直接升压作用。静脉注射rHuEPO后，给药后18至24小时血清EPO水平呈单指数下降。皮下注射rHuEPO的吸收较慢，血清EPO水平相对较低并维持48小时。所有rHuEPO抗体滴度测定均为阴性。除血红蛋白和血细胞比容显著升高外，未出现具有临床意义的变化。未观察到高血压、惊厥或血栓形成事件。在10名受试者中观察到的不良事件，均未被认为具有临床意义，且没有受试者因不良事件退出研究。
