title: Pharmacokinetic and pharmacodynamic profiles of extended dosing of epoetin alfa in anemic patients who have chronic kidney disease and are not on dialysis.
abstract: OBJECTIVE
  Emerging evidence suggests that epoetin alfa can be administered at extended intervals of up to 4 wk. This open-label, randomized study was performed to characterize the pharmacokinetic and pharmacodynamic profiles of four dosing regimens of epoetin alfa administered subcutaneously in anemic patients who had chronic kidney disease and were not on dialysis.
  
  
  METHODS
  Thirty-eight patients, enrolled from nine centers in the United States, were > or =18 yr of age and had hemoglobin <11.0 g/dl and GFR 12 to 60 ml/min per 1.73 m(2). Patients received one of four epoetin alfa dosing regimens: 50 IU/kg three times per week, 10,000 IU once weekly, or 20,000 IU every 2 wk for 36 d or 40,000 IU every 4 wk for 64 d. Each regimen provided a similar dosage of epoetin alfa over 4 wk. Dosage adjustments were not permitted.
  
  
  RESULTS
  Drug exposure to epoetin alfa over 4 wk, based on area under the curve, was somewhat higher with the extended interval regimens compared with the three-times-weekly regimen. Mean change in hemoglobin during the study period was similar for all regimens. No patients were transfused. Three patients experienced five serious adverse events, none of which was considered treatment related.
  
  
  CONCLUSIONS
  Extended dosing interval regimens of epoetin alfa yielded modest pharmacokinetic differences but a similar pharmacodynamic response, suggesting that less frequent, higher dosages of epoetin alfa may be as effective as the current three-times-weekly regimen in anemic patients who have chronic kidney disease and are not on dialysis.
authors.affiliation: Ortho Biotech Clinical Affairs, LLC, 430 Route 22 East, Bridgewater, NJ 08807, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: McGowan
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Vaccaro
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Beaver
authors.forename: Joseph
authors.initials: J
authors.lastname: Massarella
authors.forename: Marsha
authors.initials: M
authors.lastname: Wolfson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D002908:Chronic Disease; D003956:Dialysis; D004334:Drug Administration Schedule; D000068817:Epoetin Alfa; D004906:Erythrocyte Count; D004921:Erythropoietin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006397:Hematinics / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007279:Injections, Subcutaneous; D007674:Kidney Diseases / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins; D017701:Reticulocyte Count; D016896:Treatment Outcome; D014481:United States
chemical_list: D006397:Hematinics; D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa