Carcinogenicity testing of eliglustat in mice and rats.
Regul Toxicol Pharmacol
; 73(1): 401-12, 2015 Oct.
Article
em En
| MEDLINE
| ID: mdl-26232705
ABSTRACT
Eliglustat is a novel glucosylceramide synthase inhibitor for long-term oral treatment of type 1 Gaucher disease (GD1), an inherited metabolic disorder. The carcinogenic potential of this drug has been evaluated in lifetime carcinogenicity bioassays in mice and rats. Administration of eliglustat to Swiss CD-1 mice at 0, 10, 25 or 75 mg/kg/day for 104 weeks by dietary admixture did not influence survival or bodyweight evolution, or produce any clinical indication of poor condition. At histopathology, no increases in tumor incidence for any tumor type were attributed to treatment with eliglustat. Systemic exposure to eliglustat was confirmed by a reduction in circulating levels of glucosylceramide. Administration of eliglustat to Sprague-Dawley rats by oral gavage for 105 weeks at 0, 10, 25 or 75 mg/kg/day (males) or 103 weeks at 0, 5, 15 or 50 mg/kg/day (females) did not affect survival rates, but resulted in reduced bodyweight evolution in male rats (-18% at high dose), indicating that the MTD had been achieved. At histopathology, no increases in tumor incidence were attributed to treatment with eliglustat. Systemic exposure was confirmed by toxicokinetic analyses. In conclusion, eliglustat was not carcinogenic to mice or rats in standard lifetime bioassays.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirrolidinas
/
Carcinógenos
/
Inibidores Enzimáticos
/
Neoplasias
Limite:
Animals
Idioma:
En
Revista:
Regul Toxicol Pharmacol
Ano de publicação:
2015
Tipo de documento:
Article