Pharmacokinetic and pharmacodynamic properties of methoxy polyethylene glycol-epoetin beta are unaffected by the site of subcutaneous administration

C.E.R.A. (methoxy polyethylene glycol-epoetin beta), a continuous erythropoietin receptor activator, differs from traditional erythropoiesis-stimulating agents in its pharmacokinetic and receptor binding properties. This phase I, randomized, open-label, single-center, single-dose, 3-way crossover study in 42 healthy volunteers compared the pharmacokinetic and pharmacodynamic profile of CE.R.A. 3.0 mu g/kg after subcutaneous injection into the abdomen, arm, or thigh. The pharmacokinetic profile was similar at all 3 injection sites, with a prolonged apparent elimination half-life from 160 to 164 hours, area under the concentration-time curve from 4088 to 4323 ng-h/mL, and clearance/bioavoilability from 0. 64 to 0. 68 mL/h/kg. C.E.R.A. produced a sustained erythropoietic response, and the pharmacodynamic profile (area under the reticulocyte count-time curve and maximum increase in reticulocyte count) was similar for all sites. C.E.R.A. was generally well tolerated, regardless of the administration site. This study suggests that C.E.R.A. has the potential to offer a choice of injection sites in clinical practice. The long half-life may permit effective anemia management with extended dosing intervals. Phase X clinical studies support the role of C.E.R.A. in managing anemia in patients with chronic kidney disease.