Pharmacokinetics of intravenous recombinant human erythropoietin in patients with chronic renal failure

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Abstract
In order to improve our understanding of the dose‐concentration and concentration‐effect relationships, the pharmacokinetics of recombinant erythropoietin were studied after the initial dose (n = 6) and after repeated doses (n = 9) administered intravenously in patients with chronic renal failure. Several venous blood samples were collected before (to obtain the baseline concentration) and after an intravenous dose of erythropoietin. A radioimmunoassay was used to determine the erythropoietin concentration in the samples. The apparent volume of distribution at steady state was 4.2 ± 0.9 1 (initial dose) and 3.7 ± 0.61 (repeated dosing), which is close to the assumed plasma volume in these patients. The half‐life was 5.3 ± 1.3 h and 5.8 ± 1.2 h in the two groups, respectively, and is therefore too short for any accumulation to be expected when dosing three times per week. Consequently, no difference in baseline values could be detected between the groups. The clearance of erythropoietin in the groups was estimated to be 11.4 ± 7.0 ml min −1 and 7.8 ± 3.8 ml min−1, respectively. Erythropoietin kinetics did not differ after repeated dosing compared to the single initial dose. Intravenous administration of erythropoietin will result in high peak concentrations followed by a rapid decline to basal values.