单硝酸异山梨酯对尼索地平在大鼠体内药代动力学的影响（英文）

Influence of isosorbide-5-mononitrate on pharmacokinetics of nisoldipine in rat plasma

目的:考察单硝酸异山梨酯对尼索地平在大鼠体内药代动力学的影响。方法:12只健康雄性SD大鼠随机分成2组(分别为单独和联合给药组),用LC-MS/MS法测定血浆中尼索地平的浓度。结果:大鼠单独给予尼索地平和联合给予单硝酸异山梨酯后,尼索地平主要药动学参数如下:Cmax分别为(8.67±3.97)μg/L和(9.21±5.02)μg/L,AUC0-t分别为(19.6±9.9)μg·h·L-1和(25.7±13.7)μg·h·L-1,t1/2分别为(2.26±0.66)h和(3.17±1.41)h,AUC0-∞分别为(23.7±9.7)μg·h·L-1和(32.4±12.3)μg·h·L-1。统计学分析显示,单独用药与联合用药组药动学参数无统计学差异(P>0.05)。结论:单硝酸异山梨酯不影响尼索地平在大鼠体内药动学过程,为临床安全有效地联用单硝酸异山梨酯和尼索地平提供了实验依据。

AIM：To investigate the influence of isosorbide-5-mononitrate on pharmacokinetics of nisoldipine in rats.METHODS：Healthy male SD rats were administered with nisoldipine or in combination with isosorbide-5-mononitrate,and the plasma concentrations of nisoldipine were determined by LC-MS/MS.RESULTS：Maximum plasma concentration of nisoldipine alone was（8.67±3.97）μg/L compared with（9.21±5.02）μg/L for the combination.The elimination half-lives were（2.26±0.66）h and（3.17±1.41）h for nisoldipine alone and in combination,respectively.The area under the concentration-time curve of nisoldipine alone was（19.6± 9.9）μg·h·L-1 as opposed to（25.7 ±13.7）μg·h·L^-1 in combination.The statistic analysis showed there were no significant differences between two groups（P 0.05）.CONCLUSION：Isosorbide-5-mononitrate does not affect the pharmacokinetics of nisoldipine in SD rats, which providing experimental basis for clinical application of isosorbide-5-mononitrate and nisoldipine.