Allon Michael, Kleinman Kenneth, Walczyk Michael, Kaupke Charles, Messer-Mann Louise, Olson Kurt, Heatherington Anne C, Maroni Bradley J
University of Alabama at Birmingham, 35294, USA.
Clin Pharmacol Ther. 2002 Nov;72(5):546-55. doi: 10.1067/mcp.2002.128374.
The aim of this multicenter, randomized, open-label study was to compare the pharmacokinetic and pharmacodynamic profiles of darbepoetin alfa, a new erythropoiesis-stimulating protein, and recombinant human erythropoietin (epoetin) after repeated intravenous dosing in patients with chronic kidney disease receiving hemodialysis.
Forty-seven patients were randomized to receive darbepoetin alfa administered once weekly (n = 17) or 3 times weekly (n = 15) or epoetin administered 3 times weekly (n = 15) for up to 52 weeks. Pharmacokinetic profiles were measured during weeks 1 and 12 and at hemoglobin steady state (defined as a hemoglobin concentration within the target range for 4 consecutive weeks after week 12 with no change in study drug dose) or between weeks 36 and 40, whichever occurred first.
At each of the 3 time points evaluated, the terminal half-life of darbepoetin alfa was 2 to 3 times longer and the clearance approximately 4 times slower than those of epoetin. At week 12, the terminal half-life was 23.4 hours with darbepoetin alfa once weekly, 18.3 hours with darbepoetin alfa 3 times weekly, and 8.0 hours with epoetin 3 times weekly. The pharmacokinetics of darbepoetin alfa was not dependent on dose or time. Mean hemoglobin values at steady state were all approximately 11 g/dL, within the target range of 9.0 to 13.0 g/dL. Safety analyses revealed no differences between darbepoetin alfa and epoetin.
The pharmacokinetic and pharmacodynamic profiles and safety data for darbepoetin alfa demonstrate that it can be administered less frequently than epoetin in patients with chronic kidney disease receiving hemodialysis, thus simplifying anemia management.
这项多中心、随机、开放标签研究的目的是比较新型促红细胞生成蛋白——达比加群酯与重组人促红细胞生成素（促红细胞生成素）在接受血液透析的慢性肾病患者中重复静脉给药后的药代动力学和药效学特征。
47名患者被随机分为三组，分别接受每周一次（n = 17）或每周三次（n = 15）的达比加群酯治疗，或每周三次（n = 15）的促红细胞生成素治疗，持续52周。在第1周和第12周以及血红蛋白稳定状态（定义为第12周后连续4周血红蛋白浓度在目标范围内且研究药物剂量无变化）或第36周和第40周之间（以先出现者为准）测量药代动力学特征。
在评估的三个时间点中的每一个时间点，达比加群酯的终末半衰期比促红细胞生成素长2至3倍，清除率约慢4倍。在第12周时，每周一次达比加群酯的终末半衰期为23.4小时，每周三次达比加群酯为18.3小时，每周三次促红细胞生成素为8.0小时。达比加群酯的药代动力学不依赖于剂量或时间。稳定状态下的平均血红蛋白值均约为11 g/dL，在9.0至13.0 g/dL的目标范围内。安全性分析显示达比加群酯和促红细胞生成素之间无差异。
达比加群酯的药代动力学和药效学特征及安全性数据表明，在接受血液透析的慢性肾病患者中，达比加群酯的给药频率可低于促红细胞生成素，从而简化贫血管理。
