尼索地平对单硝酸异山梨酯在大鼠体内药动学的影响

目的：考察尼索地平对单硝酸异山梨酯在大鼠体内药动学的影响。方法：将大鼠随机均分为单用（单硝酸异山梨酯5.4mg·kg-1）组和联用（单硝酸异山梨酯5.4mg·kg-1＋尼索地平5.4mg·kg-1）组,每组6只,灌胃给药。于给药前和给药后8.0h内眼球后静脉丛取血,用高效液相色谱法测定血浆中单硝酸异山梨酯的浓度,以DAS软件处理,并用非房室模型统计矩方法计算和比较药动学参数。结果：单用组与联用组单硝酸异山梨酯的药动学参数为：t1/2分别为（2.309±0.916）、（1.324±0.500）h,cmax分别为（2.292±0.700）、（2.735±0.439）mg·L-1,AUC0～8h分别为（3.339±0.663）、（4.152±0.719）mg·h·L-1,Vd分别为（0.881±0.378）、（0.462±0.202）L,均符合二室模型;其中与单用组比较,联用组t1/2、Vd明显减小（P〈0.05）,其他参数无明显变化。结论：尼索地平可加快单硝酸异山梨酯在大鼠体内的消除。

Effects of Nisoldipine on Pharmacokinetics of Isosorbide-5-mononitrate in Rats

OBJECTIVE：To investigate the effect of nisoldipine on pharmacokinetics of isosorbide-5-mononitrate in rats.METHODS：Rats were divided into single drug group（isosorbide-5-mononitrate 5.4 mg·kg-1,i.g.）and drug combination group（isosorbide-5-mononitrate 5.4mg·kg-1 ＋nisoldipine 5.4mg·kg-1,i.g.）with 6 rats in each group.The blood samples were collected from venous plexus before medication and within 8.0 h after medication.The plasma concentrations of isosorbide-5-mononitrate were determined by HPLC.Pharmacokinetic parameters were calculated with non-compartmental model using DAS software.RESULTS：The main pharmacokinetic parameters of 2 groups were as follows：t 1/2：（2.309±0.916）vs.（1.324±0.500）h,c max：（2.292±0.700）vs.（2.735±0.439）mg·L-1,AUC 0～8 h：（3.339±0.663）vs.（4.152±0.719）mg·h·L-1,V d：（0.881±0.378）vs.（0.462±0.202）L.They were in line with two-compartmental model.Compared with single drug group,t 1/2 and V d of drug combination group decreased significantly（P0.05）,while other parameters had no obvious change.CONCLUSION：Nisoldipine promotes the elimination of isosorbide-5-mononitrate in rats.