| Autor: |
Bugelski, Peter, Nesspor, T., Spinka-Doms, T., Makropoulos, D., Eirikis, E., Fisher, J., Volk, A., Shamberger, K., James, I., Fisher, P., Pool, C., Jang, H., Miller, B., Huang, C., Heavner, G., Knight, D., Ghrayeb, J., Scallon, B. |
| Zdroj: |
Blood; November 2005, Vol. 106 Issue: 11 p4261-4261, 1p |
| Abstrakt: |
CNTO 528 is a member of a group of novel stimulants of erythropoiesis that has recently entered clinical trials. Although CNTO 528 bears no sequence homology to erythropoietin (EPO), it is an EPO receptor agonist, capable of rescuing EPO-dependent cells from apoptosis in vitro and stimulating erythropoiesis in vivo. The purpose of these experiments was to explore the pharmacodynamics and pharmacokinetics of CNTO 528 in normal rats and to evaluate its efficacy in rat models of anemia. In vitro, CNTO 528 was approximately 10-fold less potent on a molar basis than recombinant human EPO (rhEPO) in stimulating the growth of UT-7EPO cells. Despite the lower in vitro potency, when compared to rhEPO and darbepoetin in normal rats, a single subcutaneous dose of CNTO 528 caused a longer-lived reticulocytosis and a longer-lived increase in hemoglobin. Also, CNTO 528 caused only minor changes in red cell distribution width (RDW) or mean cell volume (MCV) led to the release of mature reticulocytes and had no effect on mean platelet volume (MPV). We have also shown that CNTO 528 was efficacious in rat models of anemia and in a rat model of pure red cell aplasia. Taken together, our data show that CNTO 528 is a novel stimulant of erythropoiesis in rats. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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