Halstenson C E, Macres M, Katz S A, Schnieders J R, Watanabe M, Sobota J T, Abraham P A
Department of Medicine, Hennepin County Medical Center, the College of Pharmacy, Minneapolis 55415.
Clin Pharmacol Ther. 1991 Dec;50(6):702-12. doi: 10.1038/clpt.1991.210.
Different recombinant human erythropoietin products have been developed. Although they appear to have similar pharmacokinetics and function, these have not been directly compared. This randomized, double-blind, four-period crossover study compared the pharmacokinetics and pharmacodynamics of intravenous and subcutaneous epoetin alfa and epoetin beta in 18 normal male volunteers. As a control, three subjects received placebo treatment. After intravenous administration, the steady-state volume of distribution and beta-phase volume of distribution of epoetin beta were 7.7% and 16.9% larger than for epoetin alfa (p less than 0.05). The terminal elimination half-life after intravenous administration of epoetin beta was 20% longer than the terminal elimination half-life of epoetin alfa. After subcutaneous administration there was a delayed drug absorption with epoetin beta compared with epoetin alfa (p less than 0.05). There was a small but significantly greater absolute reticulocyte response after subcutaneous epoetin beta compared with subcutaneous epoetin alfa. The findings support differences in the pharmacokinetics and function of epoetin alfa and beta that are possibly caused by differences in their glycosylation.
已经研发出了不同的重组人促红细胞生成素产品。尽管它们似乎具有相似的药代动力学和功能，但尚未进行直接比较。这项随机、双盲、四期交叉研究比较了18名正常男性志愿者中静脉注射和皮下注射阿法依泊汀和贝他依泊汀的药代动力学和药效学。作为对照，三名受试者接受了安慰剂治疗。静脉给药后，贝他依泊汀的稳态分布容积和β相分布容积比阿法依泊汀分别大7.7%和16.9%（p<0.05）。静脉注射贝他依泊汀后的终末消除半衰期比阿法依泊汀长20%。皮下给药后，与阿法依泊汀相比，贝他依泊汀的药物吸收延迟（p<0.05）。皮下注射贝他依泊汀后的绝对网织红细胞反应虽小但显著大于皮下注射阿法依泊汀。这些发现支持阿法依泊汀和贝他依泊汀在药代动力学和功能上存在差异，这可能是由它们糖基化的差异所导致的。
