Objective To establish a micro volume blood sampling method via the saphenous vein for pharmacokinetic studies(PK studies)in mice, aiming at reducing animal use and alleviate animal pain in in vivo procedures. Methods CD-1 mice were intravenously or orally administered with model compounds A,B,C and D.Blood samples were collected by both the micro-sampling method and regular method at the same time points,and used for the measurement of plasma drug concentration. Pharmacokinetic parameters obtained from each method were compared. Results For each of the four compounds,plasma PK profiles generated by micro-sampling via saphenous vein were in good accordance with those by the regular sampling method via retro-orbital venous plexus. Conclusions Our newly developed micro-sampling blood collecting method can replace the regular blood collecting method used in pharmacokinetic studies in mice. It can significantly improve animal welfare by alleviating animal pain. The volume of blood withdrawn can be reduced by 80%,and the number of mice used for the pharmacokinetic studies can be reduced by 65%.%目的 在体内药物代谢动力学实验中,为了减少动物的使用量(3R-Reduction)以及减轻动物的痛苦(3R-Refinement),本研究首次建立了小鼠后肢隐静脉进行微量采血的方法,利用较以往灵敏5~10倍的生物分析技术进行药代动力学研究.方法 给予雄性CD-1小鼠静脉注射或者口服灌胃模型化合物A、B、C、D,通过隐静脉微量采血法(所需动物数量少、采血量少、动物承受痛苦轻微)以及常规眼眶后静脉丛采血法(所需动物数量多、采血量较多、动物承受痛苦较严重)两种采血方法,分别在给药后的相同时间点进行采血,测定各组的小鼠血浆药物浓度,并对计算所得的药代动力学参数进行比较.结果 对于所有模型化合物,隐静脉微量采血与眼眶后静脉丛常规采血法所获得的主要药代动力学参数一致,无明显差异.结论 在小鼠药代动力学实验中隐静脉微量采血法完全可以替代现有的常规眼眶后静脉丛采血法,从而显著地减少了动物使用量、减轻了动物所承受的痛苦,采血量减少了80%,动物使用量减少了65%,更加符合动物福利3R原则.
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