硝苯地平对兔体内地高辛药代动力学的影响

Influence of nifedipin on the pharmacokinetics of digoxin in rabbits

目的研究家兔服用硝苯地平后对地高辛血药浓度及药代动力学的影响,为临床合理用药提供参考。方法选取8只新西兰兔,雌雄各半,进行自身交叉对照实验。一组口服硝苯地平5天后口服地高辛,另一组仅口服地高辛,均于给药后于耳缘静脉采血0.7 ml,洗净2周后,两组交叉给药,采血后血样经离心处理后取血清用荧光偏振免疫分析法测定血药浓度;使用DAS2.0程序计算药代动力学参数,SPSS统计处理软件进行统计学处理。结果合用硝苯地平后,地高辛达峰浓度升高33%(P<0.05);药-时曲线下面积增加40%(P<0.05);半衰期延长72%(P<0.05);总清除率减少40%。结论服用硝苯地平后可以使地高辛在兔体内的药动学过程发生明显改变,表明地高辛与硝苯地平合用时,应谨慎地观测地高辛的生理效应,并且注意监测地高辛血药浓度。

Objective To study the influence of nifedipin on the pharmaeokinetics of digoxin in rabbits and to provide reference for rational administration in clinical practice. Methods Eight rabbits, half male and half female, were divided into two groups randomly. Digoxin of 60 ng/kg was administered to animals from one group and plasma concentration of digaoxin was determined in 8 rabbits after digoxin administration alone or together with nifedipine. Digoxin concertration in plasma was determined by fluorescence polarization i mmunoassay. Pharmacokinetics parameters were calculated using DAS 2.0 software and statistics analysis was performed by SPSS 10.0 software. Results Nifedipine increased Cmax, t1/2 and AUC of digoxin by 33%, 72% and 40%, respectively and decreased mean plasma clearance by 40%, Conclusion Combination of digaoxin with nifedipine represents a clinically significant drug interaction. Plasma digaoxin concentration should be oberserved when patients intake nifedipine.