Evaluation of paracetamol toxicity in the cynomolgus monkey
Evaluation of paracetamol toxicity in the cynomolgus monkey作者机构：Centre for Drug Safety Evaluation and ResearchShanghai Institute of Materia Medica Global Safety AssessmentAstraZeneca R&D BostonMAUSA and UK
出 版 物：《中国药理学与毒理学杂志》 (Chinese Journal of Pharmacology and Toxicology)
年 卷 期：2013年第3期
页 面：544-544页
核心收录：
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
摘 要：Paracetamol(acetominophen,APAP) was administered orally in a rising dose protocol to 2 male and 2 female Cynomolgus monkeys to determine the Maximum Tolerated dose(MTD) for subsequent toxicology *** the subsequent repeat dose study involving 6 monkeys,no dose-limiting toxicity was seen at up to 900 mg·kg-1.d-1 APAP for 14 *** analysis showed that plasma exposure rose,albeit less than proportionally,with increasing *** were some fluctuations in clinical chemistry and haematology parameters,but these were not dose-related,and there were no compound-related findings observed *** monkeys at 900 mg·kg-1.d-1 had a 5 cm,gas filled segment in their large intestine that was considered *** profiling of the urine showed parent and glucuronidated APAP,but the cysteinyl conjugate which would be anticipated if the monkey has similar metabolism to rats and man was notably *** opens the possibility that metabolism in the cynomolgus monkey differs from that in the other species,and shows that the cynomolgus monkey is a poor model for investigating paracetamol-mediated toxicity in humans.
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