Cheung W, Minton N, Gunawardena K
The R W Johnson Pharmaceutical Research Institute, Raritan, NJ 08869, USA.
Eur J Clin Pharmacol. 2001 Aug;57(5):411-8. doi: 10.1007/s002280100324.
To compare the pharmacokinetics, pharmacodynamics, and tolerance of epoetin alfa administered subcutaneously (s.c.) once weekly (q.w.) and three times weekly (t.i.w.).
An open-label, randomized, parallel-design study was conducted in 36 healthy adults with hemoglobin (Hb) levels of 11.7 14.0 g/dl for women and 13.0-14.8 g/dl for men. Subjects were randomized to epoetin alfa 150 IU/kg s.c. t.i.w. or 40,000 IU s.c. q.w. for 4 weeks. Serum erythropoietin concentrations were measured using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetic parameters [peak serum concentration (Cmax), mean predose trough concentration (Cmin), time to Cmax (tmax), clearance after s.c. administration (CL/F), area under the plasma concentration time curve (AUC), and terminal elimination half-life (t 1/2)] were calculated using model-independent methods. Mean changes from baseline and AUC of percentage reticulocytes, Hb, and total red blood cell (RBC) concentrations over the 1-month study period were calculated.
The Cmax values for serum epoetin alfa q.w. were six times and AUC(0-168) values three times that of the t.i.w. regimen. Time profiles of changes in percentage reticulocytes, Hb, and total RBC over 1 month were similar between regimens. The rate of increase in Hb was similar for the two groups, and both groups exhibited a 3.1-g/dl increase in mean Hb levels from baseline through day 29. Changes in ferritin levels were generally similar between groups and reflected expected use of iron stores for Hb production. Epoetin alfa administered t.i.w. or q.w. was well tolerated and no serious adverse events occurred.
The pharmacodynamic responses were equivalent between groups despite expected differences in total erythropoietin exposure. These results indicate that the epoetin alfa 150 IU/kg t.i.w. and 40,000 IU q.w. regimens can be considered clinically equivalent.
比较皮下注射（s.c.）促红细胞生成素α每周一次（q.w.）和每周三次（t.i.w.）的药代动力学、药效学及耐受性。
对36名健康成年人进行了一项开放标签、随机、平行设计的研究，女性血红蛋白（Hb）水平为11.7 - 14.0 g/dl，男性为13.0 - 14.8 g/dl。受试者被随机分为皮下注射促红细胞生成素α 150 IU/kg每周三次（t.i.w.）组或40,000 IU每周一次（q.w.）组，共4周。使用经过验证的酶联免疫吸附测定（ELISA）法测定血清促红细胞生成素浓度。采用非模型方法计算药代动力学参数[血清峰值浓度（Cmax）、给药前平均谷浓度（Cmin）、达峰时间（tmax）、皮下给药后清除率（CL/F）、血浆浓度-时间曲线下面积（AUC）和终末消除半衰期（t1/2）]。计算1个月研究期内网织红细胞百分比、Hb和总红细胞（RBC）浓度相对于基线的平均变化及AUC。
促红细胞生成素α每周一次给药的血清Cmax值是每周三次给药方案的6倍，AUC(0 - 168)值是其3倍。两种给药方案在1个月内网织红细胞百分比、Hb和总RBC的变化时间曲线相似。两组Hb升高速率相似，两组从基线到第29天的平均Hb水平均升高3.1 g/dl。两组铁蛋白水平变化总体相似，反映了预期用于Hb生成的铁储备利用情况。促红细胞生成素α每周三次或每周一次给药耐受性良好，未发生严重不良事件。
尽管促红细胞生成素总暴露量存在预期差异，但两组间药效学反应相当。这些结果表明，促红细胞生成素α 150 IU/kg每周三次和40,000 IU每周一次的给药方案在临床上可视为等效方案。
