rasH2转基因小鼠与C57BL/6小鼠单次灌胃F3SM动力学参数比较  

Comparison on pharmacokinetic parameters in blood of 2 species mouse after single ig administration of F3SM

作　　者：刘悦[1] 孔琦[1] 樊星[1] 呼丹[1] 董延生[1] 马华智[1] 吴纯启[1] 钟武[1] 王全军[1] 丁日高[1] 

机构地区：[1]军事医学科学院毒物药物研究所抗毒药物与毒理学国家重点实验室(军事医学科学院)国家北京药物安全评价研究中心,北京100850

出　　处：《药物评价研究》2015年第3期279-283,共5页Drug Evaluation Research

基　　金：重大新药创制科技重大专项(2013ZX09302303;2012ZX09301003-001-008)

摘　　要：目的比较C57BL/6小鼠(简称C57小鼠)和rasH2转基因小鼠(TgrasH2小鼠)单次给予相同剂量受试药物F3SM后,代谢动力学参数的差异,观察两种动物对于F3SM的代谢动力学的一致性。方法选用相同周龄的C57小鼠和TgrasH2小鼠各4只,ig给予相同剂量(60mg/kg)的F3SM羧甲基纤维素钠溶液。在给药后5、15、30min及1、3、10、24h各时间点进行采血,采血量≥40μL,从血样中分离出10μL血浆,采用LC-MS/MS方法对样品的药物浓度进行检测,用软件计算得出AUC(0-t)、MRT(0-t)、t1/2、Tmax和Cmax,用配对t检验进行差异性分析。结果对C57小鼠和rasH2转基因小鼠的AUC(0-t)、MRT(0-t)、t1/2、Tmax和Cmax进行配对t检验,显示差异无显著性;二者药时曲线也大致相近。结论单次给药后,C57小鼠和TgrasH2小鼠对药物F3SM的代谢特征无显著差异,提示C57小鼠与TgrasH2小鼠对本药物的代谢特征相似,提示在开展TgrasH2小鼠研究中,可首先采用C57小鼠进行毒性预探研究。Objective To compare the pharmacokinetic parameters between C57BL/6 mice（C57 mice） and rasH2 transgenic mice（TgrasH2 mice） after a single ig administration of the same dose of test drug F3 SM, to evaluate the consistence of the two animals for F3 SM in metabolism kinetics. Methods Picked the same week-old C57 mice and TgrasH2 mice, four mice per species. Following a single ig administration of the same dose（60 mg/kg） of sodium carboxymethyl cellulose solution F3 SM, the blood samples（≥ 40 μL） were collected at 0.5 min, 15, 30, 60 min,, and 10 and 24 h after administration. Plasma（10 μL） was separated out from each of the blood samples, determined by LC-MS/MS for the concentration of F3 SM. AUC（0-t）, MRT（0-t）, t1/2, Tmax, and Cmax were carried out by software and Paired Sample T test was used for difference analysis. Results Paired Sample T test of two kinds mice on AUC（0-t）, MRT（0-t）, t1/2, Tmax, and Cmax turned out（P 〉0.05）, showing no significant difference, and drug concentration-time profile of the two species mice were roughly similar. Conclusion After a single administration, C57 and TgrasH2 mice have no significant difference in drug metabolism characteristics, suggesting that C57 and TgrasH2 mice have the similar metabolic characteristics of this drug, and we could conduct toxicity prediction research first with C57 mice when carrying out research by TgrasH2 mice.

关 键 词：致癌性试验模型 TgrasH2小鼠 C57小鼠 代谢动力学 

分 类 号：R965[医药卫生—药理学]