Pharmacokinetics and pharmacodynamics of r-HuEPO

Recombinant human erythropoietin (r-HuEPO) is now widely used in patients with anaemia resulting from chronic renal failure (CRF), and its value is being tested in a variety of other anaemic conditions. Both the intravenous (IV) and subcutaneous (SC) routes of administration of r-HuEPO are effective despite widely differing bioavailability and pharmacokinetic profiles. Following IV injection, r-HuEPO occupies an apparent volume of distribution equivalent to the plasma volume and has an estimated elimination half-life of 2-13 hours, which tends to increase dose-dependently. SC administration of r-HuEPO is characterised by a prolonged absorption phase, and peak plasma concentrations are typically reached between 12 and 18 hours after injection. In chronic anaemic conditions unrelated to CRF, the pharmacodynamic response to r-HuEPO appears to depend on the baseline serum erythropoietin level, bone marrow responsiveness and iron availability. Algorithms which may help to predict the therapeutic efficacy of r-HuEPO in the individual patient are currently being developed.