학술논문
Assessing the Carcinogenicity of Vadadustat, an Oral Hypoxia-Inducible Factor Prolyl-4-Hydroxylase Inhibitor, in Rodents.
Document Type
Article
Source
Subject
*HYPOXIA-inducible factors
*RATS
*VASCULAR endothelial growth factors
*CARCINOGENICITY
*RODENTS
*SPRAGUE Dawley rats
*
*
*
*
*
Language
ISSN
0192-6233
Abstract
Vadadustat is an investigational oral hypoxia-inducible factor (HIF) prolyl-4-hydroxylase inhibitor to treat anemia due to chronic kidney disease (CKD). Some studies suggest that HIF activation promotes tumorigenesis by activating angiogenesis downstream of vascular endothelial growth factor, while other studies suggest that elevated HIF activity may produce an antitumor phenotype. To evaluate the potential carcinogenicity of vadadustat in mice and rats, we dosed CByB6F1/Tg.rasH2 hemizygous (transgenic) mice orally by gavage with 5 to 50 mg/kg/d of vadadustat for 6 months and dosed Sprague-Dawley rats orally by gavage with 2 to 20 mg/kg/d for approximately 85 weeks. Doses were selected based on the maximally tolerated dose established for each species in previous studies. The tumors that were identified in the studies were not considered to be treatment-related for statistical reasons or within the historical control range. There was no carcinogenic effect attributed to vadadustat in mice or rats. [ABSTRACT FROM AUTHOR]