Pharmacokinetics and erythropoietic response to human recombinant erythropoietin in healthy men.

To assess the safety, pharmacokinetics, and erythropoietic responses to human recombinant erythropoietin (epoetin beta), single intravenous doses (10, 50, 150, and 500 IU/kg) were administered at monthly intervals to 16 healthy subjects in a two-panel, placebo-controlled, double-blind ascending-dose trial. A 1000 IU/kg dose was subsequently administered in an open manner. Epoetin concentrations were determined in serum and urine by radioimmunoassay. Reticulocyte, hemoglobin, and hematocrit values were serially measured after each dose. Mean epoetin apparent half-lives ranged from 4.42 to 11.02 hours. The apparent volume of distribution was between 40 and 90 ml/kg, consistent with plasma water, and the apparent clearance values ranged from 4 to 15 ml/kg/hr, with both parameters having the highest values at the 10 IU/kg dose level. Clearance tended to decrease as a function of dose. Maximum reticulocyte counts were dose-dependent and occurred 3 to 4 days after the epoetin dose. Epoetin was well tolerated, and no antibodies were detected.

RCT Entities:   Population Interventions Outcomes