Subcutaneous versus Intravenous Epoetin in Patients with Renal Failure

Summary The purpose of this overview was to compare the bioavailability of epoetin (recombinant human erythropoietin) with its activity after subcutaneous injection. Weighted means for pharmacokinetic parameters of epoetin were calculated from 15 studies with a total of 160 human subjects. After intravenous injection, total body clearance was 0.13 ml/min/kg, and terminal half-life 6.7 hours. After subcutaneous injection, maximum serum concentrations were found after 16.7 hours; the terminal half-life of 22.7 hours was determined by the rate of absorption from the subcutaneous depot. In patients with renal failure, the subcutaneous maintenance doses were 61% of the equipotent intravenous doses. The bioavailability after subcutaneous injection was 33.6%. The average steady-state serum concentrations of epoetin during intravenous therapy were 4.9 times higher than during subcutaneous treatment with equipotent doses. This discrepancy may partly be explained by the high initial concentrations after an injection that contribute little to the therapeutic effect, and partly by an underestimation of the bioavailability by the formation of active metabolites with low affinity for the antibody used in the radioimmunoassay. We conclude that the bioavailability of epoetin given via different routes of administration does not permit the estimation of equipotent doses.