Pharmacokinetics and pharmacodynamics of epoetin alfa once weekly and three times weekly

摘要: Objective: To compare the pharmacokinetics, pharmacodynamics, and tolerance of epoetin alfa administered subcutaneously (s.c.) once weekly (q.w.) three times (t.i.w.). Methods: An open-label, randomized, parallel-design study was conducted in 36 healthy adults with hemoglobin (Hb) levels 11.7–14.0 g/dl for women 13.0–14.8 g/dl men. Subjects were randomized to 150 IU/kg s.c. t.i.w. or 40,000 IU q.w. 4 weeks. Serum erythropoietin concentrations measured using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetic parameters [peak serum concentration (Cmax), mean predose trough (Cmin), time Cmax (tmax), clearance after administration (CL/F), area under plasma concentration–time curve (AUC), terminal elimination half-life (t 1/2)] calculated model-independent methods. Mean changes from baseline AUC percentage reticulocytes, Hb, total red blood cell (RBC) over 1-month period calculated. Results: The values six AUC(0–168) that regimen. Time profiles RBC 1 month similar between regimens. rate increase Hb two groups, both groups exhibited 3.1-g/dl through day 29. Changes ferritin generally reflected expected use iron stores production. Epoetin well tolerated no serious adverse events occurred. Conclusion: pharmacodynamic responses equivalent despite differences exposure. These results indicate regimens can be considered clinically equivalent.