Preclinical safety demonstration of the human recombinant erythropoietin HEBERITRO registered

• Published in: Biotecnología aplicada Vol. 22; no. 4; pp. 273 - 278
• Main Authors: Bacardi, D M, Cosme, K, Gutierrez, A, Porras, D N, Urquiza, D, Merino, N, Suarez, J, Vazquez, A, Howland, I, Perez-Caballero, M
• Format: Journal Article
• Language: English; Spanish
• Published: 01.12.2005
• ISSN: 0864-4551

Erythropoietin (EPO) is a glycoprotein that appears in blood as a response to hypoxia, acting on bone marrow to increase the production of erythrocytes. This glycoprotein is produced mainly by the kidneys; and its biosynthesis and release are stimulated by the reduction of tissue oxygenation and/or the reduction of the mass of erythrocytes. Here we report the results of the preclinical evaluation of the safety of HEBERITRO registered , commercial name for the recombinant human erythropoietin (rhEPO) produced by the Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba, through a comparative study of acute toxicity with EPREX registered , a commercial homologue, and a study of local tolerance. The product was administered subcutaneously into Sprague-Dawley rats, at doses of 10, 30 and 60 times the therapeutic dose (TD) for the comparative acute toxicity assay, and at the TD, 10 and 20 times this value, and placebo for the local tolerance assay. The dosage and inoculation schemes were designed for measuring the short-term toxicity of HEBERITRO registered after a single administration at high dosages, and the irritating potential for the subcutaneous tissue after seven daily inoculations. No signs of toxicity or morphological alterations were detected in the animals during the assays, and there were no histological changes in the organs under study. Based on these results, we conclude that this product does not induce signs of toxicity or local reactions at the administration site in the established dosage and under our experimental conditions.