The Open Hematology Journal

2010, 4 : 17-20
Published online 2010 December 30. DOI: 10.2174/1874276901004010017
Publisher ID: TOHJ-4-17

Pharmacokinetics and Pharmacodynamics of an EPO-Mimetic Fusion Protein in a Model of Chronic Renal Insufficiency Anemia

Connie M. Kliwinski , Dorie Makropoulos , Debora Kwok , Amy L. Volk , Kim Foster , Thomas Nesspor , Chichi Huang and Peter J. Bugelski
Biotechnology Toxicology, RC-1 Centocor R&D 145 King of Prussia Road, Radnor, PA 19087, USA;

ABSTRACT

Renal insufficiency is commonly associated with an erythropoietin (EPO) dependent anemia. CNTO 530 is an EPO-mimetic antibody fusion protein with EPO-receptor agonist activity. The pharmacokinetics and pharmacodynamic activity of CNTO 530 were evaluated in a rat model of chronic renal insufficiency (CRI) induced anemia. Following 5/6 nephrectomy and 13 -17 weeks of stabilization, rats received a single subcutaneous (SC) dose of saline or CNTO 530 (0.03, 0.1, or 0.3 mg/kg). CNTO 530 caused dose-dependent reticulocytosis and long-lived increases in red blood cells, hemoglobin, and hematocrit. After receiving a dose of 0.1 mg/kg, red cell indices increased and remained within normal range for 44 days. Pharmacokinetic analysis showed that clearance of CNTO 530 increased 1.4 fold and terminal t1/2 and AUC decreased 1.6 fold in CRI rats compared to controls. CNTO 530 is active in a CRI rat model of anemia and widely spaced treatments with CNTO 530 may be sufficient to combat anemia.

Keywords:

Partial nephrectomy, recombinant proteins, erythropoietin, rats..