Pharmacokinetics of recombinant human erythropoietin in children with chronic renal failure.

Abstract

Basal erythropoietin (Epo) levels and single dose-pharmacokinetics of recombinant human erythropoietin (rhuEpo) were investigated in 8 predialysis (PD) patients (mean age 11.6 +/- 1.4 years) and in 8 patients on continuous ambulatory peritoneal dialysis (CAPD) (mean age 12.7 +/- 0.6 years). Basal Epo levels were found to be 1.0 +/- 0.0 mu/ml in PD group, 1.6 +/- 0.7 mu/ml in CAPD group and 8.5 +/- 1.8 mu/ml in control group. Following administration of 50 mu/kg rhuEpo (s.c.) serum Epo concentration (Cmax) was 23.2 +/- 2.5 mu/ml in 18.5 +/- 2.6 hours (tmax) in PD patients and 9.9 +/- 0.8 mu/ml in 26.8 +/- 7.7 hours in CAPD patients. Mean elimination half-lives (t1/2) were 13.3 +/- 1.9 hours and 13.5 +/- 3.0 hours in PD patients and CAPD patients, respectively. The volume of distribution (Vd) was 840.0 +/- 100.0 ml/kg; the clearance (Epo Cl) was 37.0 +/- 5.5 ml/kg/hour in PD patients. These values were significantly lower in PD patients than in CAPD patients (p < 0.05) (Vd; 1500 +/- 240.0 ml/kg; Epo Cl 110 +/- 30.0 ml/kg/hour). During the course of CAPD, more efficient clearance of uraemic toxins that inhibit erythropoiesis and more rapid extraction of erythropoietin by erythroid precursors may cause higher Vd in CAPD patients than in PD patients.