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Efficacy and safety of deferoxamine conjugated to hydroxyethyl starch. 1992

S A Mousa, and R C Ritger, and R D Smith
Pharmaceuticals and Biotechnology Research Division, Du Pont Merck Pharmaceutical Company, Wilmington, Delaware 19880-0400.

The efficacy and safety of deferoxamine conjugated to hydroxyethyl starch (HES-DFO) was evaluated in an in vitro rat cardiac membrane lipid peroxidation (CMLP) assay and in a swine model of regional myocardial ischemia/reperfusion injury in comparison to DFO. The rat CMLP results demonstrate that HES-DFO is at least as potent as DFO (IC50 = 10 and 13 microM, respectively). HES-DFO given intravenously (i.v.) at the equivalence of 25 mg/kg and 100 mg/kg DFO in a swine model of regional myocardial ischemia [20-min left anterior descending coronary artery (LAD) occlusion followed by 60-min reperfusion] showed no significant changes in hemodynamics as compared with DFO at 25 mg/kg i.v. In addition, HES-DFO was at least as potent as DFO with regard to recovery of regional segment shortening function (%SS). Furthermore, both HES-DFO and DFO significantly reduced tissue water content (edema) in the area at risk (AAR). We conclude that conjugation of DFO to HES improves the safety without any interference in the efficacy of DFO.

UI MeSH Term Description Entries
D008297 Male Males
D008566 Membranes Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures. Membrane Tissue,Membrane,Membrane Tissues,Tissue, Membrane,Tissues, Membrane
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D003327 Coronary Disease An imbalance between myocardial functional requirements and the capacity of the CORONARY VESSELS to supply sufficient blood flow. It is a form of MYOCARDIAL ISCHEMIA (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. Coronary Heart Disease,Coronary Diseases,Coronary Heart Diseases,Disease, Coronary,Disease, Coronary Heart,Diseases, Coronary,Diseases, Coronary Heart,Heart Disease, Coronary,Heart Diseases, Coronary
D003676 Deferoxamine Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form. Desferrioxamine,Deferoxamine B,Deferoxamine Mesilate,Deferoxamine Mesylate,Deferoxamine Methanesulfonate,Deferoximine,Deferrioxamine B,Desferal,Desferioximine,Desferrioxamine B,Desferrioxamine B Mesylate,Desferroxamine,Mesilate, Deferoxamine,Mesylate, Deferoxamine,Mesylate, Desferrioxamine B,Methanesulfonate, Deferoxamine
D004487 Edema Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE. Dropsy,Hydrops,Anasarca
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic
D006895 Hydroxyethyl Starch Derivatives Starches that have been chemically modified so that a percentage of OH groups are substituted with 2-hydroxyethyl ether groups. Hetastarch,Elohes,HAES-steril,Hemohes,Hespan,Hydroxyethyl Starch (130 KD-0.4 Substitution),Hydroxyethyl Starch 130-0.4,Hydroxyethylated Starches,Pentafraction,Pentaspan,Pentastarch,Plasmasteril,Starches, 2-Hydroxyethyl,2-Hydroxyethyl Starches,Derivatives, Hydroxyethyl Starch,Hydroxyethyl Starch 130 0.4,Starch Derivatives, Hydroxyethyl,Starches, 2 Hydroxyethyl,Starches, Hydroxyethylated
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013552 Swine Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog

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