Proof-of-concept study on improved efficacy of rHuEPO administered as a long-term infusion in rats

BACKGROUND: Human recombinant erythropoietin (rHuEPO) is often used in the treatment of diseases associated with a decreased production of red blood cells (RBC), such as chronic renal failure. rHuEPO is typically administered as an intravenous or subcutaneous (SC) injection every few days. The low minimum effective concentration (MEC) of rHuEPO, compared to the concentrations observed after standard doses, suggests that a low dose of the drug administered as a long-term infusion should be efficacious. This study aimed to compare the efficacy observed after a single subcutaneous administration of rHuEPO with that observed after a long-term infusion of rHuEPO via implanted osmotic pumps at a similar or lower dose. MATERIALS AND METHODS: In this study three rats received rHuEPO as a single SC injection at a dose of 1350 IU/kg, nine via osmotic pumps at a rate of 0.25, 0.5 and 1 IU/kg and at a total dose of 333 IU/kg, 667 IU/kg, 1333 IU/kg. Three rats served as a control group. The erythropoietin concentrations, RBC count and hemoglobin were measured. RESULTS: An increase in RBC count and hemoglobin was observed after SC infusion of rHuEPO. The baseline corrected area under the effect curve for hemoglobin and RBC count was more than 10-times higher for the SC infusion than for a single SC administration with a comparable dose. CONCLUSIONS: This study demonstrates that administration of rHuEPO as a long-term infusion at a rate ensuring MEC allows to achieve a high efficacy of therapy using relatively small doses of the drug.