目的 比較C57BL/6小鼠(簡稱C57小鼠)和rasH2轉(zhuǎn)基因小鼠(Tg rasH2小鼠)單次給予相同劑量受試藥物F3SM后, 代謝動力學(xué)參數(shù)的差異, 觀察兩種動物對于F3SM的代謝動力學(xué)的一致性。方法 選用相同周齡的C57小鼠和Tg rasH2小鼠各4只, ig給予相同劑量(60 mg/kg)的F3SM羧甲基纖維素鈉溶液。在給藥后5、15、30 min及1、3、10、24 h各時間點進行采血, 采血量≥40 μL, 從血樣中分離出10 μL血漿, 采用LC-MS/MS方法對樣品的藥物濃度進行檢測, 用軟件計算得出AUC_(0-t)、MRT_(0-t)、t_1/2、T_max和C_max, 用配對t檢驗進行差異性分析。結(jié)果 對C57小鼠和rasH2轉(zhuǎn)基因小鼠的AUC_(0-t)、MRT_(0-t)、t_1/2、T_max和C_max進行配對t檢驗, 顯示差異無顯著性;二者藥時曲線也大致相近。結(jié)論 單次給藥后, C57小鼠和Tg rasH2小鼠對藥物F3SM的代謝特征無顯著差異, 提示C57小鼠與Tg rasH2小鼠對本藥物的代謝特征相似, 提示在開展Tg rasH2小鼠研究中, 可首先采用C57小鼠進行毒性預(yù)探研究.

Objective To compare the pharmacokinetic parameters between C57BL/6 mice (C57 mice) and rasH2 transgenic mice (Tg rasH2 mice) after a single ig administration of the same dose of test drug F3SM, to evaluate the consistence of the two animals for F3SM 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 F3SM, 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 F3SM. AUC_(0-t), MRT_(0-t), t_1/2, T_max, and C_max 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), t_1/2, T_max, and C_max 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 Tg rasH2 mice have no significant difference in drug metabolism characteristics, suggesting that C57 and Tg rasH2 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 Tg rasH2 mice.

重大新藥創(chuàng)制科技重大專項(2013ZX09302303, 2012ZX09301003-001-008)