SUBCUTANEOUS VERSUS INTRAVENOUS EPOETIN IN PATIENTS WITH RENAL-FAILURE - OVERVIEW OF THE PHARMACOKINETICS AND COMPARISON WITH THE PHARMACODYNAMIC ACTIVITY

The purpose of this overview was to compare the bioavailability of epo etin (recombinant human erythropoietin) with its activity after subcut aneous injection. Weighted means for pharmacokinetic parameters of epo etin were calculated from 15 studies with a total of 160 human subject s. After intravenous injection, total body clearance was 0.13 ml/min/k g, and terminal half-life 6.7 hours. After subcutaneous injection, max imum serum concentrations were found after 16.7 hours; the terminal ha lf-life of 22.7 hours was determined by the rate of absorption from th e subcutaneous depot. In patients with renal failure, the subcutaneous maintenance doses were 61% of the equipotent intravenous doses. The b ioavailability after subcutaneous injection was 33.6%. The average ste ady-state serum concentrations of epoetin during intravenous therapy w ere 1.9 times higher than during subcutaneous treatment with equipoten t doses. This discrepancy may partly be explained by the high initial concentrations after an injection that contribute little to the therap eutic effect, and partly by an underestimation of the bioavailability by the formation of active metabolites with low affinity for the antib ody used in the radioimmunoassay. We conclude that the bioavailability of epoetin given via different routes of administration does not perm it the estimation of equipotent doses.