富含铁元素食物对非洛地平片在Beagle犬体内药动学的影响  

Effects of foods rich in Fe^(3+) on pharmacokinetics of felodipine tablets in Beagle dogs

作　　者：陈仕云 何勇 于艳英 彭扶云 高永好 吴宗好 CHEN Shiyun;HE Yong;YU Yanying;PENG Fuyun;GAO Yonghao;WU Zonghao(Analytical&Testing Center,Hefei University,Hefei,Anhui230601,China;HefeiHuafang Pharmaceutical Science&Technology Co.,Ltd.,Hefei,Anhui230088,China)

机构地区：[1]合肥学院分析测试中心,安徽合肥230601 [2]合肥华方医药科技有限公司,安徽合肥230088

出　　处：《安徽医药》2019年第9期1737-1740,共4页Anhui Medical and Pharmaceutical Journal

摘　　要：目的研究高铁饮食对非洛地平在Beagle犬体内药动学影响。方法采用随机、开放、单剂量给药、双交叉试验设计。12条健康Beagle犬采用随机数字表法分为两组,每组6条,分别空腹和餐后服用5 mg非洛地平片,给药前后按不同采血时间点采集血样,采用液相色谱-质谱联用(HPLC?MS/MS)法测定血浆中非洛地平浓度,用DAS3.2.8软件计算药动学参数。结果空腹与餐后主要药动学参数如下:Cmax(12.59±2.17)、(7.13±2.96)ng/mL,tmax(1.25±0.24)、(1.32±0.35)h,t1/2(1.1±0.69)、(1.2±0.72)h,AUC0-1(2 19.46±5.23)、(11.87±3.85)ng·h^-1·mL^-1,AUC0-∞(20.69±5.75)、(12.76±4.18)ng·h^-1·mL^-1。以AUC0-12计算,实验组的相对生物利用度F为(61.0±12.7)%。与对照组相比,实验组Beagle犬的生物利用度偏低,而且达峰浓度也降低,说明食物中Fe3+抑制了非洛地平药物的吸收。结论高铁饮食可显著降低非洛地平片在Beagle犬体内的吸收程度,但不影响其吸收速度。Objective To investigate the effect of ferrum diets on pharmacokinetics of Felodipine in Beagle dogs.Methods A ran?domized,open?label,single dose and two?way crossover clinical study was conducted.Twelve healthy Beagle dogs were randomly di?vided into two groups,then 5 mg of felodipine were admitted respectively before and after meal.Blood samples were collected at dif?ferent time points before and after drug administration.The concentration of felodipine in plasma was determined by HPLC?MS/MS.The pharmacokinetic parameters were calculated by DAS3.2.8.Results The main pharmacokinetic parameters were as follows:Cmax(12.59±2.17)and(7.13±2.96)ng·mL^-1,tmax(1.25±0.24)and(1.32±0.35)h,t1/2(1.1±0.69)and(1.2±0.72)h,AUC0-12h(19.46±5.23)and(11.87±3.85)ng·h^-1·mL^-1,AUC0-∞(20.69±5.75)and(12.76±4.18)ng·h^-1·mL^-1,Respectively according to AUC0-12h,the relative bioavailability of felodipine in the experimental group was(61.0±12.7)%.Compared to the control group,the bioavailability of felodipine in the experimental group was low and the peak concentration decreased.Conclusion High ferrum Diets can signifi?cantly reduce the extent of absorption of felodipine in Beagle dogs,however,with no influence on the absorption rate of felodipine.

关 键 词：非洛地平 药代动力学 高效液相色谱-串联质谱法 食物药物相互作用 

分 类 号：R54[医药卫生—心血管疾病]