目的通过布比卡因人血清白蛋白微球家兔皮下给药的药效学和药动学研究,考查布比卡因人血清白蛋白微球的体内释药行为和神经阻滞效果。方法以家兔为实验对象,以注射剂为对照组,采用改良的反相高效液相色谱法测定体内布比卡因血药浓度,以针刺疼痛反应圈半径大小评价其麻醉效果。结果药动学实验结果表明,注射剂组血药浓度达峰时间短(t_max=0.313h),浓度高(c_max=2.374μg·mL^-1),药物代谢速度快。由于微球的突释作用和随后的缓慢释放,使得微球组血药浓度出现双峰现象,并长时间维持较低水平,实验组MRT较对照组明显延长(P<0.01)。药效学实验表明,微球组皮下给药最大麻醉圈直径显著小于注射剂对照组(P<0.01),而微球组局麻持续时间较对照组明显延长(P<0.01)。结论微球组与注射剂组相比,药物扩散少,局部麻醉作用持续时间长,说明微球组在体内具有明显的缓释作用和较好的安全性。

OBJECTIVE To investigate the distribution in vivo and nerve blockage of bupivacaine hydrochloride human serum albumin microspheres(Bupi-HAS-MS) after subcutaneous adminstration by pharmacokinetics and pharmacodynamics study.METHODS RP-HPLC method was used to determinate the bupivacaine concentration in rabbit plasma and the diameter with no reaction to needling method was used to evaluate the analgestic effect of Bupi-HAS-MS.RESULTS The analysis of pharmacokinetics showed that t_max in control group was shorter than that of Bupi-HAS-MS group and c_max was higher than that of MS group significantly.The mean retention time(MRT) of Bupi-HAS-MS group was prolonged compared to that of the injection group (P< 0.01) .The result of pharmacodynamics demonstrated that the biggest anaesthetic circle diameter of Bupi-HAS-MS group was bigger than that of injection group (P< 0.01) and anaesthetic time of Bupi-HAS-MS group was prolonged compared to that of the injection group (P<0.01) evidently. CONCLUSION There are remarkable sustained release and good safety by Bupi-HAS-MS subcutaneous administration.