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。
Abstract
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 chromatography-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 pharmacokinetic parameters of the two groups were as follows: Cmax: (513.36?56.02) and (585.21?77.52) ng/ml, t1/2: (1.30?0.51) and (1.51?0.65) h, AUC0-t: (433.70?50.98) and (721.16?218.09) ng/(h穖l), CL/F: (38.02?5.63) and (25.9?5.18) L/(h穔g).The pharmacokinetics parameters of AUC0-t 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 pharmacokinetics of bisoprolol with extending of absorption and excretion in rats.
关键词
氨氯地平 /
比索洛尔 /
药动学 /
液相色谱-串联质谱
Key words
amlodipine /
bisoprolol /
pharmacokinetics /
LC-MS/MS
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] 陈灏珠.实用内科学[M].13版.北京:人民卫生出版社,2009:1625-1640.
[2] 张维忠.降压联合治疗的理论和实践问题[J].中华心血管病杂志,2006,34(4):385-386.
[3] 杨世杰,杨宝峰,王怀良.药理学[M].北京:人民卫生出版社,2005:335.
[4] Meredith P A,Eilliott H L.Clinical pharmacokinetics of amlodipine[J].Clin Pharmacokinet,1992,22(1):22-31.
[5] Fogari R, Zoppi A,Corradi L ,et al.β-blocker effects on plasmalipids during prolonged treament of hypertensive patients with hypercholesteremia[J].J Cardiovasc Pharmacol,1999,33(4):534-539.
[6] 郭 鹏.左旋氨氯地平联合比索洛尔治疗老年高血压性肥厚型心肌病28例疗效观察[J]. 临床合理用药,2011,7(4):54-55.
[7] 彭 澄,何晓峰,刘慎微.氨氯地平联合比索洛尔治疗肾性高血压23例[J].医药导报,2009, 28(11): 1456-1458.