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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 the pharmacokinetics of manidipine hydrochloride in rats. Methods The rats were randomly divided into 0.9 mg · kg -1 mannitol hydrochloride group and 0.9 mg · kg -1 manniptin hydrochloride group and 0.9 mg · kg -1 lisinopril group. Venous blood was taken within 0-12.0 h after drug administration, and the plasma concentration of manidipine hydrochloride was determined by LC-MS / MS. The pharmacokinetic parameters were calculated by DAS 2.0, and SPSS 17.0 was used for statistical analysis. Results The pharmacokinetic parameters of Manidipine hydrochloride alone and in combination were as follows: ρmax were (144.6 ± 24.39) μg · L-1 and (150.2 ± 24.63) μg · L-1, respectively; AUC0-t were (489.4 ± 190.5) μg · h · L-1 and (573.3 ± 196.4) μg · h · L-1, and the AUC0-∞ were 566.7 ± 233.4 μg · h · L-1 and 666.4 ± 283.0 μg · H · L-1 and tmax were (0.8 ± 0.21) h and (1.05 ± 0.57) h respectively, and the Vz / F were (1.84 ± 0.82) L · kg -1 and (1.56 ± 0.65) L · kg -1 , Cl / F were (7.90 ± 3.67) L · h-1 · kg-1 and (6.28 ± 1.69) L · h-1 · kg-1, respectively. There were no significant differences in tmax, AUC0-t, Cl / F, ρmax, AUC0-∞, Vz / F and Cl / F between the two groups (P> 0.05). Conclusion Lisinopril has no effect on the pharmacokinetics of Manidipine Hydrochloride in rats, suggesting that it is not necessary to adjust the dose and time interval of Manidipine in clinical combination therapy.