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及后，血浆中药物达峰显著性差异(P0.05)浓度Cmax(P0.05)。 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 pharmacokinetic 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 pharmacokinetic 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(P0.05), and the peak concentration Cmax of bulk drug was higher than sustained release pellets after a dose conversion(P0.05). CONCLUSIONS Compared 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 a sustained release performance of this preparation. KEY WORDS: tamsulosin hydrochloride; sustained release pellets; LC/MS/MS; pharmacokinetics 介绍 盐酸坦洛新，化学名为(R)(-)5-｛2-[[2-(2-乙氧苯基)乙醚基]胺基]-2-甲基｝-乙基-2-甲氧基苯磺酰胺盐酸盐属肾上腺素α1受体亚型α1A的阻断剂，尿道、膀胱颈部及前列腺存在的α1受体具有高选择性阻断作用降低平滑肌张力，降低下尿路阻力，用于治疗前列腺增生所致的异常排尿症状，如尿频、夜尿增多、排尿困难等。 图1 坦洛新化学结构式 Fig. 1 Chemical structure of tamsulosin 1 材料与仪器 1.1 药品与试剂 盐酸坦洛新原料药(批纯度99.2%)，盐酸坦洛新缓释微丸(批每188 mg含盐酸坦洛新0.2 mg)，均由江苏恒瑞医药股份有限公司提供。内标物SHR117616(批纯度95.3%，由本公司化学合成组合成)。HPLC甲醇购自Thermofisher公司，水为屈臣氏蒸馏水，其余试剂为分析纯，购自国药集团化学试剂有限公司。 1.2 试验动物 健康成年Beagle犬