静脉注射沙利度胺及其前药和美014后大鼠体内药动学研究

目的:研究沙利度胺及其前药和美014经静脉注射给药后沙利度胺在大鼠体内的药动学情况。方法:大鼠单次尾静脉注射给予等摩尔数的沙利度胺或和美014后,采集不同时间点的血液样品及注射和美014后各组织样品,用高效液相色谱法测定血浆和组织中的沙利度胺的浓度,用3p97药动学程序拟合并计算、比较药动学参数。结果:大鼠静脉注射沙利度胺或和美014后体内沙利度胺t1/2β约为159～170min,表观分布容积Vd约为0.758～1.062L·kg-1,各药动学参数两两比较无明显差异。沙利度胺在大鼠体内各组织中分布广泛,其中以在肝、肠、肾、脑等组织中浓度较高。结论:大鼠静脉注射沙利度胺或和美014后药动学特征无明显差异,和美014在体内可快速完全转化成沙利度胺,沙利度胺在大鼠体内分布快、广。

Pharmacokinetic Study on Hemay014 and Thalidomide in Rats by Intravenous Administration

OBJECTIVE： To study pharmacokinetics of thalidomide following intravenously administration of thalidomide and Hemay014 in rats. METHODS： Rats were given same dose of thalidomide and Hemay014 at one time via tail vein. The blood and tissue samples were collected at different time points after administration of thalidomide. The concentration of thalidomide in plasma and tissue were determined by HPLC and pharmacokinetic parameters were fitted, calculated and compared with 3p97 pharmacokinetics program. RESULTS： After administration of thalidomide and Hemay014, the pharmacokinetic parameters were as follows： tf/2β = 159 - 170 min; Vd = 0.758 - 1.062 L·kg^-1. There was no significant difference among parameters. Thalidomide widely distributed in various tissues, of which it showed high concentration in liver, intestinal, kidney, brain and so on. CONCLUSIONS： There is rarely difference of pharmacokinetic parameters in rats after administration of thalidomide and Hemay014 （i.v.）. Hemay014 can be transferred into thalidomide then deliver to tissues rapidly and widely.