Single-dose Pharmacokinetics of Recombinant Human Erythropoietin in Patients with Various Degrees of Renal Failure

Abstract

The pharmacokinetic profile of recombinant human erythropoietin (rHuEpo) was studied after a single intravenous dose of 150 U/kg in ten patients with various degrees of renal function: group I, creatinine clearance >80 ml/min, n=2; group II, creatinine clearance 10–50 ml/min, n=6; group III, creatinine clearance n=2. Erythropoietin concentrations in serum and urine samples obtained over 48 h were measured by RIA. rHuEpo was cleared from circulation in an exponential fashion, the half-life ranged from 6.5 to 12.7 h (mean 9.03 h) and was not different between the groups. The apparent volume of distribution varied from 0.041 to 0.0991/kg (mean 0.0701/kg) this corresponds to 1.5 times the plasma volume and was unrelated to kidney function. Renal clearance (groups I, II) accounted for less than 3% of total body clearance, both parameters were unaffected by decreasing renal function. These results indicate that, in accordance with animal data, the elimination of rHuEpo occurs mainly through non-renal mechanisms.