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, Peter J. Bugelski
Identifiers and Pagination:Year: 2010
First Page: 17
Last Page: 20
Publisher Id: TOHJ-4-17
Article History:Received Date: 20/09/2010
Revision Received Date: 12/10/2010
Acceptance Date: 14/10/2010
Electronic publication date: 30/12/2010
Collection year: 2010
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.