Pharmacokinetics of recombinant human erythropoietin in children with renal failure

Abstract

The single-dose pharmacokinetics of recombinant human erythropoietin (rHuEpo; 40 units/kg1) were investigated in children (9-16 years) with end-stage renal failure. After an intravenous (i.v.) dose, serum rHuEpo concentrations declined in a monoexponential manner with a mean half-life (t1/2) of 5.6 +/- 3 h (+/- SEM; n = 9). Serum clearance and the apparent volume of distribution were estimated to be 10.1 +/- 0.9 ml h-1 kg-1 and 79.5 +/- 5.0 ml kg-1 (n = 9) respectively. Subcutaneous (s.c.) delivery resulted in serum values that peaked at 10 h, and thereafter concentrations declined slowly with a t1/2 of 21.1 +/- 4.5 h (n = 9). Serum rHuEpo concentrations were maximal at 14 h after i.p. administration and the t1/2 was 9.5 +/- 1.0 h (n = 3). The mean fraction absorbed of SC rHuEpo was 0.40 whereas after i.p. administration this fraction was only 0.17. These results show that after both s.c. and i.p. delivery, disposition of the hormone is rate-limited by absorption, and bioavailability for these extravascular routes is poor. In addition, comparison of the results with those available for adults indicates that rHuEpo is better absorbed but more rapidly cleared in children.