Chronic pharmacological and safety evaluation of Hematide, a PEGylated peptidic erythropoiesis-stimulating agent, in rodents.

Basic & Clinical Pharmacology & Toxicology
Kathryn W WoodburnDaniel Norton

Abstract

Hematide is a synthetic peptide-based, PEGylated erythropoiesis-stimulating agent, which is being developed for the chronic treatment of anaemia associated with chronic renal failure. To support the safety of long-term dosing of chronic renal failure patients, a comprehensive toxicology programme was implemented including rat subchronic and chronic studies. Rats were administered 0, 0.1, 1 and 10 mg/kg of Hematide every 3 weeks for 3 months via subcutaneous injection or for 6 months via intravenous injection. The dosing period was followed by a 6-week follow-up period. The primary pharmacology of Hematide resulted in erythroid polycythemia as measured by elevated haemoglobin levels that were time- and dose-dependent. The pharmacology profiles were similar regardless of administration route. For example, for male rats at Day 90, subcutaneous dosing resulted in haemoglobin increases of 2.7, 4.5 and 6.9 g/dl for 0.1, 1 and 10 mg Hematide/kg respectively, compared to 2.8, 5.7 and 7.4 g/dl increases for intravenous dosing. Histopathological changes were related to the prolonged severe polycythemia induced in normocythemic animals administered an erythropoiesis-stimulating agent. The findings included extramedullary haematopoiesis in...Continue Reading

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Citations

Dec 23, 2009·Nanomedicine·Keitaro SouWilliam T Phillips
Aug 6, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Xue-Lian GongBo-Jun Yuan
May 1, 2012·Journal of Parasitology Research·Sushrut Kamerkar, Paul H Davis
Mar 3, 2010·Expert Opinion on Therapeutic Patents·Francis Dumont, Pierre Bischoff
Aug 1, 2009·Expert Review of Hematology·Francesco Locatelli, Lucia Del Vecchio
Jun 9, 2011·Drug and Chemical Toxicology·Kathryn W WoodburnSudhir A Shah
Feb 18, 2010·Expert Opinion on Emerging Drugs·Ugo Testa
May 4, 2010·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·Elise M LewisKathryn W Woodburn
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Mar 20, 2013·Expert Opinion on Pharmacotherapy·Holger Schmid
Dec 23, 2011·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Kathryn W WoodburnYoshihiko Tagawa
Sep 21, 2013·Drug Discovery Today·Maryam Hamzeh-MivehroudSiavoush Dastmalchi
Jan 16, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Kathryn W WoodburnYoshihiko Tagawa
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Oct 22, 2021·FEMS Microbiology Reviews·Weronika JaroszewiczGrzegorz Węgrzyn

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Methods Mentioned

BETA
enzyme-linked immunosorbent assays

Software Mentioned

WinNonlin®

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