OBJECTIVE: 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.). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
RCT Entities:
OBJECTIVE: 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.). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Fritz Sörgel; Ursula Thyroff-Friesinger; Andrea Vetter; Bernhard Vens-Cappell; Martina Kinzig Journal: Pharmacology Date: 2008-12-22 Impact factor: 2.547
Authors: Sameer Doshi; Wojciech Krzyzanski; Susan Yue; Steven Elliott; Andrew Chow; Juan José Pérez-Ruixo Journal: Clin Pharmacokinet Date: 2013-12 Impact factor: 6.447
Authors: Anargyros Xenocostas; Wing K Cheung; Francis Farrell; Cindy Zakszewski; Marian Kelley; Andrzej Lutynski; Michael Crump; Jeffrey H Lipton; Thomas L Kiss; Catherine Y Lau; Hans A Messner Journal: Eur J Clin Pharmacol Date: 2005-03-18 Impact factor: 2.953