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

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 a nd 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 con centrations were measured using a validated enzyme-linked immunosorbent ass ay (ELISA). Pharmacokinetic parameters [peak serum concentration (C-max), m ean predose trough concentration (C-min), time to C-max (t(max)), 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 perc entage reticulocytes, Hb, and total red blood cell (RBC) concentrations ove r the 1-month study period were calculated. Results: The C-max, values for serum epoetin alfa q.w. were six times and A UC((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 s imilar 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 fr om baseline through day 29. Changes in ferritin levels were generally simil ar between groups and reflected expected use of iron stores for Hb producti on. Epoetin alfa administered t.i.w. or q.w. was well tolerated and no seri ous adverse events occurred. Conclusion: The pharmacodynamic responses were equivalent between groups de spite 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.