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Notes: Background:  Numerous prior studies have reported that a substantially higher dose of epoetin is required to maintain haemoglobin (Hb) concentration when patients are switched from a subcutaneous (SC) to intravenous (IV) route of administration. Many of the reported trials, however, involved patients who did not have adequate serum iron levels. It was hypothesized that patients with adequate iron stores who are switched from one route of administration to the other without a change in dose will experience substantially less change in their Hb concentration.Methods:  Haemodialysis patients who were iron replete (ferritin 300–800 µg/L, transferrin saturation (TSAT) 25–50%) participated in a prospective, randomized cross-over trial receiving epoetin for 3 months either by SC or IV injection followed by a further 3 months of epoetin via the other route. The principal aim was to determine changes in Hb concentration without altering the weekly epoetin dose. The secondary aim was to assess whether the frequency of dosing (once, twice or thrice weekly) influenced the Hb concentration response.Results:  Eighty-one patients (mean age 62 years, 60% male) entered the study and 15 withdrew prior to study completion. Forty-three patients began SC epoetin alfa administration (group A) and 38 on IV (group B). Median ferritin and TSAT at entry for groups A and B were 409 and 394 µg/L (NS) and 31 and 32% (NS), respectively, which remained within the target range during the study. Median epoetin doses for groups A and B were similar (90 vs 93 IU/kg per week, NS). After 3 months, the mean Hb concentration rose for group A (SC; 118.7–121.9 g/L (P = 0.03)) but it fell for group B (IV; 119.1–116.0 g/L (P = 0.019)). Following the change in route of administration, the Hb concentration for group A (IV) fell by 5.1% over 3 months (121.9–115.4, P 〈 0.001) and rose by 2.8% for group B (SC) over 3 months (116.0–119.7, P = 0.001). Similar significant changes in the Hb concentration were seen at different dosing frequencies.Conclusion:  Subcutaneuos administration of epoetin produces a significant, although slight clinical change in Hb concentration compared with IV administration in stable, iron replete, haemodialysis patients. A similar effect appears to prevail regardless of the frequency of injections given.