کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5856360 | 1131973 | 2015 | 12 صفحه PDF | دانلود رایگان |
- Eliglustat is an orally available glucosylceramide synthase inhibitor.
- Eliglustat (Cerdelga) is intended for long-term oral treatment of Gaucher disease (GD1).
- Eliglustat oral substrate reduction therapy can replace lifelong IV treatment.
- The effects of eliglustat administration were evaluated in mice and rats for up to 104 wks.
- Eliglustat was found not to be carcinogenic in lifetime carcinogenicity bioassays.
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 75Â 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 75Â mg/kg/day (males) or 103 weeks at 0, 5, 15 or 50Â mg/kg/day (females) did not affect survival rates, but resulted in reduced bodyweight evolution in male rats (â18% 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.
Journal: Regulatory Toxicology and Pharmacology - Volume 73, Issue 1, October 2015, Pages 401-412