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Pharmacokinetics and hematologic response to subcutaneous administration of recombinant human erythropoietin in
G Montini1, G Zacchello, F Perfumo
1Department of Pediatrics, Bari, Italy.
Insights
Subcutaneous recombinant human erythropoietin (rHuEPO) effectively treats anemia in children with end-stage renal failure. Low doses provide a slow release, improving hemoglobin levels with minimal side effects.
Area of Science:
- Nephrology
- Pediatrics
- Pharmacology
Background:
- Anemia is common in children with end-stage renal failure (ESRD) on peritoneal dialysis.
- Recombinant human erythropoietin (rHuEPO) is used to treat anemia in ESRD patients.
Purpose of the Study:
- To evaluate the pharmacokinetics and hematologic response to subcutaneous rHuEPO in anemic children with ESRD.
- To determine optimal dosing for achieving target hemoglobin levels.
Main Methods:
- 24 anemic children on peritoneal dialysis received initial subcutaneous rHuEPO doses of 25 IU/kg twice weekly.
- Dosage was escalated every 4 weeks if hemoglobin increase was insufficient.
- Pharmacokinetic parameters including peak concentration, AUC, half-life, and residence time were analyzed.
Main Results:
- Subcutaneous rHuEPO administration led to a rapid increase in serum concentration, with a mean peak level of 59.8 mU/ml at 9 hours.
- Eighteen of 24 children achieved increased hemoglobin levels (mean 9.4 +/- 1.7 gm/dl) after 24 weeks.
- No correlation was found between pharmacokinetic data and hemoglobin increase.
- Hypertension required management in 8 children; 6 patients discontinued treatment early.
Conclusions:
- Low-dose subcutaneous rHuEPO provides a slow drug release, effectively increasing hemoglobin levels in anemic children with ESRD.
- This treatment approach is associated with a favorable safety profile and few side effects.
Abstract:
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.