PHARMACOKINETICS OF RECOMBINANT-HUMAN-ERYTHROPOIETIN IN DIALYSIS PATIENTS AFTER SINGLE AND MULTIPLE SUBCUTANEOUS ADMINISTRATIONS

The pharmacokinetics of recombinant human erythropoietin (rhEPO) were evaluated after single intravenous and single subcutaneous administration of 40 U/kg to 8 patients with dialysis treatment. All patients suffered from renal anemia with a hematocrit less-than-or-equal-to 24% and were treated with 40 U/kg rhEPO subcutaneously, three times a week for 6 weeks. At the end of the treatment period, kinetics of rhEPO were repeated. After the initial subcutaneous rhEPO dose, the following results were obtained: maximum plasma concentration 39.5 (26.7-56.9) U/1, area under the curve (AUC) 1,122 (582-3,220) U.h.1-1 and terminal half-life 13.2 (2.6-53.1) h. The corresponding data after multiple rhEPO doses were: maximum rhEPO plasma concentration 26.3 (9.4-49.1) U/1, AUC 724 (407-1,464) U.h.1-1 and terminal half-life 14.2 (3.5-24.4) h. There were no statistical significant differences between the two investigations. From the present study, it can be concluded that after a treatment period of 6 weeks with multiple subcutaneous rhEPO doses, rhEPO absorption as well as rhEPO elimination are unchanged.