Preclinical safety and pharmacology of hematide™, a peptidic erythropoiesis stimulating agent (ESA), in rats and monkeys

被引：18

作者：

Woodburn, Kathryn W. ^{[1
]}

Schatz, Peter J. ^{[1
]}

Fong, Kei-lai ^{[2
]}

Wilson, Susan D. ^{[3
]}

Ferrell, Thomas ^{[4
]}

Spainhour, Charles B. ^{[4
]}

Norton, Daniel ^{[4
]}

机构：

[1] Affymax Inc, Palo Alto, CA 94304 USA

[2] Penn Biolab Inc, Radnor, PA USA

[3] Aclairo Pharmaceut Dev Grp Inc, Vienna, VA USA

[4] Calvert Labs, Olyphant, PA USA

来源：

DRUG AND CHEMICAL TOXICOLOGY | 2008年 / 31卷 / 02期

关键词：

erythropoiesis stimulating agents; anemia; pharmacology; safety; toxicology;

D O I：

10.1080/01480540701873186

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The pharmacology, toxicokinetics, and safety of Hematide (TM) 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.

引用

页码：229 / 244

页数：16

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