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Evaluation of the Carcinogenic Potential of Enarodustat (JTZ-951), a Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor, in 26-Week Tg.rasH2 Mouse Study and 2-Year Sprague-Dawley Rat Study.
- Source :
-
International Journal of Toxicology (Sage) . Dec2023, Vol. 42 Issue 6, p489-503. 15p. - Publication Year :
- 2023
-
Abstract
- Enarodustat (JTZ-951) is an oral hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitor for the treatment of anemia with chronic kidney disease. Carcinogenicity of enarodustat was evaluated in a 26-week repeated oral dose study in Transgenic rasH2 (Tg.rasH2) mice and a 2-year repeated oral dose study in Sprague-Dawley (SD) rats. The highest dose levels were set at 6 mg/kg in the Tg.rasH2 mouse study and at 1 mg/kg in the SD rat study based on the maximum tolerated doses in the 3-month and 6-month dose-range finding studies, respectively. Enarodustat did not increase the incidence of any tumors or affect survival in these carcinogenicity studies. Pharmacology-related findings including increases in blood RBC parameters were observed at the highest dose levels for each study. The AUC-based exposure margins as protein-unbound drug base are 16.3-/26.0-fold multiple (males/females) for Tg.rasH2 mice and 1.6-/1.1-fold multiple for SD rats when compared with the estimated exposure in human with chronic kidney disease at 8 mg/day (maximum recommended human dose). In conclusion, enarodustat was considered to have no carcinogenic potential at the clinical dose. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10915818
- Volume :
- 42
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- International Journal of Toxicology (Sage)
- Publication Type :
- Academic Journal
- Accession number :
- 173453136
- Full Text :
- https://doi.org/10.1177/10915818231190550