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目的:研究那格列奈对大鼠体内利伐沙班药动学的影响。方法:将36只SD大鼠随机分为实验组和对照组,每组18只。实验组灌胃那格列奈,每次12 mg·kg-1,每天3次;对照组灌胃等量空白溶液,每天3次,连续4 d,并于d 4灌胃30 min后,每只大鼠均灌胃利伐沙班(2.6 mg·kg-1),并于灌胃前(0 h)和灌胃后10,20,30,45 min,1,1.5,2,3,4,6,8,12,24 h眼内眦取血,LC-MS/MS法测定血浆药物浓度,绘制药时曲线,DAS 2.1.1软件拟合药动学参数,使用SPSS 17.0软件对2组的药动学参数进行统计学分析。结果:实验组与对照组主要药动学参数:AUC0-24分别为(2 572.67±1 017.61)和(1 692.75±654.72)ng·h·m L-1;AUC0-∞分别为(2 713.29±1 101.60)和(1 760.25±649.11)ng·h·m L-1;t1/2分别为(4.00±1.48)和(3.46±1.10)h;Tmax分别为(0.86±0.15)和(0.69±0.20)h;CL分别为(1.11±0.43)和(1.68±0.60)L·h-1·kg-1;V分别为(5.80±1.63)和(7.95±2.74)L·kg-1;Cmax分别为(537.83±141.35)和(438.19±122.02)ng·m L-1。t1/2无显著性差异;AUC0-24,AUC0-∞,Cmax,CL,V均有显著性差异(P<0.05)。结论:那格列奈对大鼠体内利伐沙班药动学参数有影响。
Objective: To study the effect of nateglinide on kinetics of rivaroxaban in rats. Methods: 36 SD rats were randomly divided into experimental group and control group, with 18 rats in each group. The experimental group was given nateglinide at a dose of 12 mg · kg-1 once a day for 3 times. In the control group, an equal volume of blank solution was orally administered 3 times a day for 4 days. After 30 minutes of d 4 administration, All rats were treated with rivaroxaban (2.6 mg · kg-1), and were injected intraperitoneally (0 h) and 10, 20, 30, 45 min, 1, 1.5, , 6,8,12,24 h intraocular 眦 blood, LC-MS / MS determination of plasma drug concentration, draw the drug curve, DAS 2.1.1 software fitting pharmacokinetic parameters, using SPSS 17.0 software on two groups Pharmacokinetic parameters for statistical analysis. RESULTS: The main pharmacokinetic parameters of experimental group and control group were AUC0-24 (2 572.67 ± 1 017.61) and (1 692.75 ± 654.72) ng · h · m L-1, respectively; AUC0-∞ were (2 713.29 ± 1 101.60) and (1 760.25 ± 649.11) ng · h · m L-1, respectively, and the values of t1 / 2 were (4.00 ± 1.48) and (3.46 ± 1.10) h respectively; the Tmax were (0.86 ± 0.15) and ) h and CL were (1.11 ± 0.43) and (1.68 ± 0.60) L · h-1 · kg-1, respectively, and were 5.80 ± 1.63 and 7.95 ± 2.74 L · kg- (537.83 ± 141.35) and (438.19 ± 122.02) ng · m L-1, respectively. t1 / 2 had no significant difference; AUC0-24, AUC0-∞, Cmax, CL, V were significantly different (P <0.05). Conclusion: Nateglinide affects kinetic parameters of rivaroxaban in rats.