OBJECTIVE: To compare the efficacy of intraperitoneal (i.p.) and subcutaneous (s.c.) administration of epoetin alfa in patients receiving peritoneal dialysis (PD). DESIGN: A 32-week prospective, randomized, cross-over experimental design. SETTING: Two university-based outpatient PD centers. PATIENTS: Twenty adult PD patients receiving stable doses of s.c. epoetin alfa enrolled in the study. Thirteen patients completed 32 weeks of follow-up. INTERVENTION: Patients were randomly assigned to receive either s.c. or i.p. epoetin alfa at the start of the study. Dose adjustments were made to maintain baseline hematocrit +/- 3 percentage points. Following 16 weeks of treatment, patients crossed over to the other route of administration for an additional 16 weeks. Intraperitoneal epoetin alfa was administered into an empty peritoneal cavity for approximately 8 hours before resuming dialysis. End-of-study i.p. epoetin alfa doses required to maintain target hematocrit were given twice weekly (n = 1), once weekly (n = 11), or once every other week (n = 1). All patients received iron supplements to maintain or exceed prestudy iron parameters. MAIN OUTCOME MEASURE: Prior to the study, the primary outcome measure was defined as the difference in epoetin alfa dose between i.p. and s.c. administration. RESULTS: Thirteen patients completed the study. The area under the dosing-requirement curve for i.p. epoetin alfa was larger than for s.c. administration (p = 0.0029), and the slope of the 16-week dose-requirement curve was greater for i.p. administration (p = 0.017), suggesting greater dose stability for s.c. administration. Paired analysis indicated greater i.p. intrapatient dose requirements (p < 0.0001). The mean difference in s.c. versus i.p. doses was 5000 +/- 1510 units per week. Some patients required escalating i.p. doses to maintain target hematocrit values. Iron administration and iron stores were similar in both groups. CONCLUSION: Intraperitoneal epoetin alfa may be a suitable alternative for some patients for whom s.c. dosing is undesirable. Large i.p. versus s.c. dosing differences noted in a few patients are unexplained, but may result from interpatient variability in i.p. epoetin alfa absorption. Intraperitoneal dosing into an empty peritoneum can be done safely and effectively.

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