Sergio Bassi

Pharmacokinetics and hematologic response to subcutaneous administration of recombinant human erythropoietin in children undergoing long-term peritoneal dialysis: A multicenter study

For a study of the pharmacokinetics and hematologic response of subcutaneously administered recombinant human erythropoietin (rHuEPO), 24 children (mean age, 10 years 3 months; range, 3 months to 18 years) maintained by peritoneal dialysis and with anemia caused by end-stage renal failure (mean hemoglobin level, 6.5 gm/dl; range, 4.7 to 7.9) were treated with rHuEPO administered subcutaneously at an initial dose of 25 IU/kg twice per week. After a 4-week interval, in the case of no response (hemoglobin increase < or = 1 to 1.5 gm/dl per month) the rHuEPO dosage was increased every 4 weeks according to the following schedule: 50, 75, 100, and 150 IU/kg twice per week. The administration of rHuEPO produced a rapid increase in serum concentration with a mean peak level of 59.8 mU/ml after 9 hours. Mean area under the curve to 72 hours was 2020 mU/ml per hour (range, 568 to 6609); mean elimination half-life and mean residence time were, respectively, 25.2 hours (range, 6.2 to 58.7) and 42.0 hours (range, 10.9 to 96). Of 24 children entered in the study, six had the drug suspended early because of renal transplantation (n = 1), lack of compliance (n = 4), or severe worsening of hypertension (n = 1). Eighteen patients had increased hemoglobin levels (to 9.4 +/- 1.7 gm/dl after 24 weeks of treatment). No correlation was found between the increase in hemoglobin concentration and any of the pharmacokinetic data or the peak erythropoietin level reached during the kinetic profile. Eight children required an increase of antihypertensive medications to maintain satisfactory blood pressure values. We conclude that low doses of subcutaneously administered rHuEPO slowly release the drug into the blood and satisfactorily increase hemoglobin levels with very few side effects.