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求阿伐他汀的长毒急毒资料

时间: 2008-09-18 08:50:09 作者: 来源: 字号:
希望知道的达人能告知,阿的长毒和急毒资料,!
来源:http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~NiOJNK:1

ATORVASTATIN
CASRN: 134523-00-5
For other data, click on the Table of Contents

Animal Toxicity Studies:

Non-Human Toxicity Excerpts:
A 2-year carcinogenicity study in rats at doses of 10, 30, and 100 mg/kg of body weight per day found 2 rare tumors (rhabdomyosarcoma and fibrosarcoma) in the high dose female rats (plasma drug concentration of approximately 16 times the mean human plasma drug concentration after an 80 mg oral dose). Administration of atorvastatin at 100, 200, or 400 mg/kg per day in mice (producing plasma values of 6 times the mean human drug exposure after an 80 mg dose) for 2 years resulted in a significant increase in liver adenomas in males and liver carcinomas in females.
**PEER REVIEWED**

No changes in fertility in rats were observed at does up to 175 mg/kg (15 times the human exposure). Aplasia and aspermia in the epididymis and lower epididymal weight were found at doses of 100 mg/kg per day (16 times the human exposure at the 80 mg dose). Lower testis weight was observed at doses of 30 and 100 mg/kg. Decreased sperm motility, decreased spermatid head concentration, and an increased number of abnormal sperms were observed in male rats given 100 mg/kg per day for 11 weeks prior to mating. No adverse effects on semen parameters, or reproductive organ histopathology were found in dogs given dose of 10, 40, or 120 mg/kg for 2 years.
**PEER REVIEWED**

Dostal LA et al; Toxicologist 30 (1 Pt 2): 121 (1996)] Atorvastatin is a highly efficacious HMG-CoA reductase inhibitor which produces greater reductions in LDL-cholesterol in hyperlipidemic patients than other lipid-regulating drugs. In a male fertility study, rats received 20, 100, or 175 mg/kg atorvastatin for 11 weeks prior to mating with untreated females, throughout mating, and until sacrifice. Body weight gain suppression (17% and 25%), and food consumption suppression, occurred in males at 100 and 175 mg/kg during the premating treatment period. There were no effects on copulation, fertility, # days to mating, reproductive organ weights, sperm counts, motility or morphology, and there were no effects on numbers of implants or live fetuses. In a female fertility study, rats received 20, 100, or 225 mg/kg for 2 weeks prior to mating with untreated males, throughout mating, and until Gestation Day (GD) 7. Body weight gain suppression (35%) occurred at 225 mg/kg during GD 0-8. There were no effects on estrous cycles, copulation, fertility, number of days to mating, viable litters, corpora lutea, implants, live fetuses or pre- and postimplantation loss. These studies demonstrate no adverse effects of atorvastatin on fertility and reproduction in rats.
**PEER REVIEWED**

Dostal LA et al; Teratology 50 太感谢了,Crystal_heart
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