Received December 21, 2007
Accepted on March 17, 2008

ORIGINAL ARTICLES

Pharmacokinetic and Pharmacodynamic Profiles of Extended Dosing of Epoetin Alfa in Anemic Patients Who Have Chronic Kidney Disease and Are not on Dialysis

Tracy McGowan ^*, Nicole M. Vaccaro , Jessica S. Beaver , Joseph Massarella , and Marsha Wolfson ^*1

*Ortho Biotech Clinical Affairs, LLC, Bridgewater, New Jersey; Johnson & Johnson Pharmaceutical Research & Development, LLC, Raritan, New Jersey; and Targacept, Winston-Salem, North Carolina

¹ To whom correspondence should be addressed. E-mail: mwolfsol{at}obius.jnj.com.

	Abstract

Background and objectives: 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.

Design, setting, participants, & measurements: Thirty-eight patients, enrolled from nine centers in the United States, were 18 yr of age and had hemoglobin <11.0 g/dl and GFR 12 to 60 ml/min per 1.73 m². 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.