Objective To evaluate the
pharmacokinetics of multiple
subcutaneous administration of
recombinant human erythropoietin (rhEPO) at different dosages in healthy volunteers. Methods Twelve healthy volunteers were randomized into two groups. The rhEPO were administrated subcutaneously at a dose of 50 or 150 U·kg -1 respectively on day 1,3,5,7,9,11,13 and 15. The serum concentration of rhEPO was measured by
enzyme-link-immunosorbentassay. Results The baseline serum concentration of rhEPO were from 3.75 to 13.75 mU·mL -1 with mean value of (7.92± 3.65 ) mU·mL -1 . Trough rhEPO levels (C min ) of the two groups reached a plateau after 4 to 6
dosing. AUC (0-96h) after the first dosing and last dosing in 150 U·kg -1 group were as 2.8 times and 3.0 times as that in 50 U·kg -1 group, respectively. The difference of C max between the two groups was similar to the AUC, with 3.1 times and 3.6 times higher of C max in 150 U·kg -1 group. The t max and t 1/2 after the last dosing of rhEPO in each subject did not differ significantly from that after the first dosing. Conclusion Within the dosage of 50~150 IU·kg -1 ,the increase of serum rhEPO level after multiple subcutaneous administrations was correlated with the drug dose administrated. No time-dependent pharmacokinetics were observed after multi-dosing of rhEPO. There was no drug accumulation up to seven dosing.