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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 differences in the metabolic parameters of C57BL / 6 mice (C57 mice) and rasH2 transgenic mice (TgrasH2 mice) after a single dose of F3SM, and to observe the metabolic motility of F3SM in two animals Consistency of learning. Methods Four C57 mice and TgrasH2 mice of the same age were used, and the same dose (60mg / kg) of F3SM sodium carboxymethyl cellulose solution was administered ig. Blood samples were collected at 5, 15, 30 min and 1, 3, 10, and 24 h after administration. The blood samples were collected at 40 μL. 10 μL of plasma was separated from the blood samples. The drug concentration was determined by LC-MS / MS , AUC (0-t), MRT (0-t), t1 / 2, Tmax and Cmax were calculated by software, and the paired t test was used for the difference analysis. Results Paired t-test showed that AUC (0-t), MRT (0-t), t1 / 2, Tmax and Cmax in C57 mice and rasH2 transgenic mice showed no significant difference; similar. Conclusion After single administration, there was no significant difference in the metabolic characteristics of F3SM between C57 mice and TgrasH2 mice, suggesting that the metabolic characteristics of this drug are similar between C57 mice and TgrasH2 mice, suggesting that in the study of TgrasH2 mice, C57 mice were used for toxicity preanalysis.