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A 26-week repeated-dose toxicity study of allisartan isoproxil in Sprague-Dawley rats

文献类型：期刊论文

作者Liu, Yongzhen1,2; Wang, Hao2; Cheng, Yumei1,2; Sun, Jingjun1; Qiao, Junwen1; Lu, Henglei1; Zhu, Liang2; Gong, Likun1; Ren, Jin1
刊名DRUG AND CHEMICAL TOXICOLOGY
出版日期2013-10
卷号36期号:4页码:443-450
关键词ALS-3 angiotensin II receptor blocker chronic progressive nephropathy rat
ISSN号0148-0545
DOI10.3109/01480545.2013.776580
文献子类Article
英文摘要Allisartan isoproxil (ALS-3) is a selective, nonpeptide blocker of the angiotensin II type 1 receptor. It is a new antihypertensive drug under development with a novel chemical structure. The aim of this study was to evaluate the potential toxicity of ALS-3 in Sprague-Dawley rats. Animals were orally administered either vehicle or ALS-3 at doses of 20, 80 and 320 mg/kg once-daily for 26 weeks, followed by a 6-week recovery period. Toxicity was assessed by mortality, clinical signs, body weight, food consumption, hematology, coagulation, serum chemistry, gross necropsy, organ weights and microscopic examination. Decreased body-weight gain was noted at 320 mg/kg/day in both sexes as well as at the 80-mg/kg/day dose in females. Food consumption was decreased at all doses in males and at 80- and 320-mg/kg/day doses in females. Decreased erythrocyte parameters (erythrocyte count, hemoglobin and hematocrit) were observed in males receiving 320 mg/kg/day. Elevated urea nitrogen (BUN), increased kidney weight, decreased heart weight and exacerbation of chronic progressive nephropathy (CPN) severity were all observed in males at 80 and 320 mg/kg/day. However, only an exacerbated incidence of CPN was observed in females at 320 mg/kg/day. All changes were reversed after the 6-week recovery period, except BUN and CPN. Based on these results, we concluded that a dose of 20 mg/kg/day was the no observed adverse effect level. The toxicity target organ was the kidney. Males were more affected than females.
WOS关键词CHRONIC PROGRESSIVE NEPHROPATHY ; LEFT-VENTRICULAR HYPERTROPHY ; HUMAN RISK-ASSESSMENT ; RECEPTOR ANTAGONIST ; RENAL-DISEASE ; HYPERTENSION ; LOSARTAN
WOS研究方向Chemistry ; Pharmacology & Pharmacy ; Toxicology
语种英语
WOS记录号WOS:000323931300008
出版者TAYLOR & FRANCIS LTD
源URL[http://119.78.100.183/handle/2S10ELR8/277453]  
专题药物安全性评价中心
通讯作者Gong, Likun
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, 501 Haike Rd,Zhang Jiang Hitech Pk, Shanghai 201203, Peoples R China
2.Shanghai Jiao Tong Univ, Sch Med, Shanghai, Peoples R China;
推荐引用方式
GB/T 7714		 Liu, Yongzhen,Wang, Hao,Cheng, Yumei,et al. A 26-week repeated-dose toxicity study of allisartan isoproxil in Sprague-Dawley rats[J]. DRUG AND CHEMICAL TOXICOLOGY,2013,36(4):443-450.
APA Liu, Yongzhen.,Wang, Hao.,Cheng, Yumei.,Sun, Jingjun.,Qiao, Junwen.,...&Ren, Jin.(2013).A 26-week repeated-dose toxicity study of allisartan isoproxil in Sprague-Dawley rats.DRUG AND CHEMICAL TOXICOLOGY,36(4),443-450.
MLA Liu, Yongzhen,et al."A 26-week repeated-dose toxicity study of allisartan isoproxil in Sprague-Dawley rats".DRUG AND CHEMICAL TOXICOLOGY 36.4(2013):443-450.

入库方式： OAI收割

来源：上海药物研究所

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