Pharmacokinetics of Recombinant Human Erythropoietin (KRN 5702) in Patients on Maintenance Hemodialysis

The present study was performed to determine the pharmacokinetic parameters of recombinant human erythropoietin (r-HuEPO: KRN 5702) in patients on maintenance hemodialysis.After a single (300 IU; n=11, 1, 500 IU; n=8, 3, 000 IU; n=12, 6, 000 IU; n=7) and multiple (3, 000 IU; n=12, 3 times per week) intravenous administration of KRN 5702, plasma concentrations of KRN 5702 were analyzed by RIA method.KRN 5702 was cleared from the circulation in an exponential fashion . Its half life (T1/2: hr) and total clearance (Cltot: ml/hr·kg) showed dose dependency (T1/2: 300 IU, 6.0; 1, 500 IU, 5.9; 3, 000 IU, 7.5; 6, 000 IU, 9.7; Cltot: 300 IU, 10.8; 1, 500 IU, 7.4; 3, 000 IU, 5.7; 6, 000 IU, 4. 1), although the apparent volume of distribution (Vd) remained unchanged.After repeated administration of KRN 5702 (3 times per week for 2 wk and 6 wk), T1/2 showed a tendency to decrease and Cltot showed a tendency to increase, although Vd remained the same. The accumulation of r-HuEPO was not observed.These results suggest the existence of bone marrow saturation of KRN 5702 when administered at high dose, and the increase of bone marrow activity, which was responsible for accelerated utilization of KRN 5702 when administered repeatedly.