盐酸坦洛新及其缓释微丸犬药代动力学研究.doc

盐酸坦洛新及其缓释微丸犬药代动力学研究
宫爱申佘高宏王丹刘悦邓炳初(上海恒瑞医药有限公司上海 200245)
摘要: 目的考察盐酸坦洛新原料药及其缓释微丸在Beagle犬体内的药动学行为,评价该缓释制剂的缓释特征。方法 Beagle犬分别口服给予盐酸坦洛新原料药及缓释微丸制剂后,采用LC/MS/MS法测定犬血浆中各时刻坦洛新的药物浓度,绘制血药浓度-时间曲线,并计算药动学参数,对主要药动学参数进行统计学分析。结果 Beagle犬口服给予盐酸坦洛新原料药及缓释微丸后,血浆中药物达峰时间tmax、消除半衰期t1/2均存在显著性差异(P<);两组峰浓度Cmax经剂量折算后存在显著性差异(P<)。结论与盐酸坦洛新原料药相比,Beagle犬口服缓释微丸后,吸收及消除速度减慢、血药峰浓度降低,符合缓释制剂的药动学行为,判断该制剂具有一定程度的缓释特征。
关键词:盐酸坦洛新;缓释微丸;LC/MS/MS;药动学
ABSTRACT: OBJECTIVE To study the ic behaviors of tamsulosin hydrochloride bulk drug and its sustained release pellets in Beagle dogs and evaluate the sustained release performance of the pellets. METHODS The plasma concentrations of tamsulosin were determined by LC/MS/MS method after a single oral administration of tamsulosin hydrochloride bulk drug and its sustained release pellets to Beagle dogs. The plasma concentration-time curves were plotted and the ic parameters were estimated and analyzed. RESULTS Differences in peak time tmax, elimination half-time t1/2 between bulk drug and sustained release pellets have been found statistically significant(P<), and the peak concentration Cmax of bulk drug was higher than sustained release pellets after a dose conversion(P<). pared with the bulk drug of tamsulosin hydrochloride, the rates of absorption and elimination were longer, and the plasma peak concentration was lower in sustained release pellets, which improved