Preclinical safety and pharmacology of Hematide, a peptidic erythropoiesis stimulating agent (ESA), in rats and monkeys.
The pharmacology, toxicokinetics, and safety of Hematide, a synthetic peptidic erythropoiesis-stimulating agent (ESA), were characterized. Hematide was given intravenously (0, 0.5, 5, and 50 mg/kg) weekly for five weeks with a 6- (rat) and 12-week (monkey) recovery period. The pharmacological action of Hematide resulted in polycythemia. Histopathology consistent with drug-induced exaggerated pharmacology was observed primarily in rats. Secondary sequelae resulting from pronounced polycythemia was considered the cause of deaths in rats and a single high-dose monkey. Toxicokinetic analysis indicated prolonged exposure. In conclusion, Hematide is a potent ESA and the safety and efficacy profile support clinical development.
Woodburn
Kathryn W
KW
Affymax, Inc, Palo Alto, California 94304, USA. Kathryn_woodburn@affymax.com
Schatz
Peter J
PJ
Fong
Kei-Lai
KL
Wilson
Susan D
SD
Ferrell
Thomas
T
Spainhour
Charles B
CB
Norton
Daniel
D
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004920:Erythropoiesis / Q000187:drug effects*; D005260:Female; D007275:Injections, Intravenous; D008252:Macaca fascicularis; D008297:Male; D010455:Peptides / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity*; D011086:Polycythemia / Q000139:chemically induced; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D010455:Peptides; C514771:hematide; D011092:Polyethylene Glycols