氨氯地平对比索洛尔在大鼠体内药动学的影响

目的探讨氨氯地平对比索洛尔在大鼠体内药动学的影响。方法 12只大鼠随机分为两组,一组给予比索洛尔灌胃,另一组给予比索洛尔与氨氯地平灌胃,分别采用液相色谱-串联质谱法测定两组大鼠血浆中比索洛尔的血药浓度。用DAS2.0程序软件拟合药动学参数,比较两者的药动学参数。结果单独给药组和联合给药组的主要药动学参数:Cmax分别为(513.36±56.02)和(585.21±77.52)ng/ml,t1/2:(1.30±0.51)和(1.51±0.65)h,AUC0-t:(433.70±50.98)和(721.16±218.09)ng/(h.ml),CL/F:(38.02±5.63)和(25.9±5.18)L/(h.kg),两组间AUC0-t和CL/F的差异具有统计学意义(P<0.05)。结论建立的液相色谱-串联质谱法专属性、准确性、灵敏度适宜。氨氯地平可延长比索洛尔在大鼠体内的吸收和排泄,对比索洛尔的药代动力学有显著影响。

Effect of amlodipine on the pharmacokinetics of bisoprolol in rats

Objective To study the effect of amlodipine on the pharmacokinetics of bisoprolol in rats. Methods Twelve rats were randomly divided into two equal groups ： A and B. Rats of group A were given bisoprolol. Rats of group B were given bisoprolol and amlodipine. Blood samples were taken from the animals for the determination of the plasma concentration of amlodipine by liquid chro- matography - mass spectrometry/mass spectrometry （ LC - MS/MS）. The pharmacokinetics parameters together were calculated using DAS program to evaluate each of the two preparations and the pharrnacokinetic parameters were statistically compared. Results The main pharmaeokinetic parameters of the two groups were as follows： Cmax： （513. 36±56. 02） and （585.21±77.52） ng/ml, tl/2 ： （1.30±0.51） and （1.51±0.65） h, AUC0-1 （433.70±50.98） and （721.16±218.09） ng/（h·ml）, CL/F： （38.02±5.63） and （25.9±5.18 ） L/（ h·kg）. The pharmacokinetics parameters of AUC0 -1 and CL/F showed significant difference between the two groups（P 〈 0.05 ）. Conclusions The LC -MS/MS method is specific and sensitive. The amlodipine has significant effect on the pharmacokineties of bisoprolol with extending of absorption and excretion in rats.