赖诺普利对盐酸马尼地平大鼠体内药动学影响

The effect of lisinopril on pharmacokinetics of manidipine in rats plasma

目的考察赖诺普利对盐酸马尼地平在大鼠体内药动学行为的影响。方法将大鼠随机分为单用盐酸马尼地平0.9 mg·kg^-1组和联用盐酸马尼地平0.9 mg·kg^-1＋赖诺普利0.9 mg·kg^-1组,于灌胃给药后0-12.0 h内取静脉血,采用LC-MS/MS法测定血浆中盐酸马尼地平的质量浓度,以DAS 2.0计算药动学参数,SPSS 17.0进行统计分析。结果单用组与联用组盐酸马尼地平的药动学参数结果为：ρmax分别为（144.6±24.39）μg·L^-1和（150.2±24.63）μg·L^-1,AUC0-t分别为（489.4±190.5）μg·h·L^-1和（573.3±196.4）μg·h·L^-1,AUC0-∞分别为（566.7±233.4）μg·h·L^-1和（666.4±283.0）μg·h·L^-1,tmax分别为（0.8±0.21）h和（1.05±0.57）h,Vz/F分别为（1.84±0.82）L·kg^-1和（1.56±0.65）L·kg^-1,Cl/F分别为（7.90±3.67）L·h^-1·kg^-1和（6.28±1.69）L·h^-1·kg^-1。两组tmax、AUC0-t、Cl/F、ρmax、AUC0-∞、Vz/F和Cl/F均无显著性差异（P〉0.05）。结论赖诺普利对盐酸马尼地平在大鼠体内药动学行为无影响,提示临床联合给药无需调整马尼地平给药剂量及时间间隔。

Objective To investigate the effect of lisinopril on pharmacokinetics of manidipine in rats plasma. Methods Rats were randomly divided into single drug group （ manidipine 0. 9 mg·kg^-1, i. g. ） and drug combination group （ manidipine 0. 9 mg·kg^-1 ＋ lisinopril 0. 9 mg·kg^-1, i. g. ）. The blood samples were collected within 0 - 12. 0 h after oral administration. The plasma concentrations of manidipine were determined by LC-MS/MS. Pharmacokinetic parameters were calculated with DAS 2. 0 software, and statistically analyzed with SPSS 17.0 software. Results The main pharmacokinetic parameters of 2 groups were as follows： Pmax = （ 144.6 ±24. 39 ） μg·L^-1 vs. （ 150. 2 ± 24.63 ）μg·L^-1 , AUC0-t （489.4 ± 190. 5 ） p.g·h·L^-1 vs. （573.3±196. 4 ） mg·h. L^-1, AUC0-∞ = （ 566.7± 233.4 ） μg·h·L^-1 vs. （666.4±283.0）μg·h·L^-1 ,tmax = （0. 8 ±0. 21）h vs. （1.05±0. 57）h,Vz/F = （1.84±0. 82）L·kg^-1 vs. （ 1.56±0. 65 ） L. kg^-1, Cl/F = （7.90±3.67 ） L·h^-1·kg^-1 vs. （ 6.28±1.69 ） L·h^-1. kg^-1. No significant difference（ P 〉 0.05 ） in the pharmacokinetic parameters of tmax, AUC0-t, Cl/F,Pmax, AUC0-∞, Vz/F, Cl/F were founded. Conclusions No significant effect of lisinopril on pharmacokinetics of manidipine in rats plasma, prompting that administration without dose adjustment manidipine and time interval in clinical.