title: Randomized cross-over comparison of intravenous and subcutaneous darbepoetin dosing efficiency in haemodialysis patients.
abstract: BACKGROUND
  Studies have consistently shown the superior dosing efficiency of subcutaneous (s.c.) compared to intravenous (i.v.) erythropoietin (r-HuEPO). Unlike r-HuEPO, data from pivotal darbepoetin trials support s.c. and i.v. dosing equivalence, however, no blinded cross-over randomized studies of s.c. and i.v. dose efficiency or intra-patient variability in response have been published.
  
  
  METHODS
  During this 12-month study, 53 haemodialysis patients were randomized to s.c. or i.v. darbepoetin for a 6-month period and then switched to the alternative route for a second 6-month period. Darbepoetin dose was titrated during the first 4-months of each period to achieve a stable haemoglobin during the final 2-month observation period of each arm.
  
  
  RESULTS
  Twenty-four patients were included in analysis. No significant difference between s.c. and i.v. administration was observed for any measured parameter. Patients achieved a non-significantly higher haemoglobin (123.6 +/- 3.76 vs 120.9 +/- 4.42 g/L, P = 0.11) from a non-significantly lower darbepoetin dose (40.8 +/- 10.7 vs 42.5 +/- 11.0 mcg/week, P = 0.23) with i.v. administration. The population-based weight normalized s.c./i.v. dose ratio was 1.04 (0.97-1.11). Despite no significant overall difference, some patients experienced changes in individual dose efficiency response. Three of 24 patients recorded a greater than 30% change, four of 24 recorded between a 20 and 30% change, and five of 24 patients recorded between a 10 and 20% change relative to i.v. dose efficiency.
  
  
  CONCLUSIONS
  This study further supports s.c. and i.v. dosing equality and that overall the more convenient i.v. route can be used with equal dosing efficiency. However, patients switching routes of administration should be monitored due to the wide range in individual response.
authors.affiliation: Renal Unit and Pharmacy Department, The Queen Elizabeth Hospital and Health Service, Adelaide, South Australia, Australia. matthew.cervelli@nwahs.sa.gov.au
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Cervelli
authors.forename: Nicholas
authors.initials: N
authors.lastname: Gray
authors.forename: Stephen
authors.initials: S
authors.lastname: McDonald
authors.forename: Melanie G
authors.initials: MG
authors.lastname: Gentgall
authors.forename: Alex P S
authors.initials: AP
authors.lastname: Disney
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D018592:Cross-Over Studies; D000068256:Darbepoetin alfa; D004921:Erythropoietin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D005260:Female; D006454:Hemoglobins; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D006435:Renal Dialysis
chemical_list: D006454:Hemoglobins; D004921:Erythropoietin; D000068256:Darbepoetin alfa