中国临床药理学杂志2017，Vol.33Issue(7)：602-604,608,4.DOI:10.13699/j.cnki.1001-6821.2017.07.008
肠道菌群变化对替格瑞洛在大鼠体内药代动力学的影响
Effect of the intestinal flora on the pharmacokinetics of ticagrelor in rats
摘要
Abstract
Objective To study the effect of intestinal flora on the pharmacokinetics of ticagrelor in rats.Methods A total of 45 SD rats were randomly divided into control group,test A group and test B group.Rats of test groups were orally given live combined bifidobacterium and lactobacillus tablets for 7 days,respectively;rats of control group were given the same volume distilled water.On day 8,ticagrelor was orally administered to all rats.Blood samples were obtained at 0.08,0.25,0.50,1,1.5,2,3,4,6,8,12,24 h after ticagrelor administration.The plasma concentration of ticagrelor was determined by LC-MS/MS.The pharmacokinetic parameters were determined by DAS 2.1.1 software and the statistic analysis was processed with SPSS 21.0 software.Results The pharmacokinetic parameters of ticagrelor in the test A group,test B group and control group were as follows:AUC0-t were (6336.24 ± 1840.46),(4444.05± 1033.43) and (4469.32 ±928.47) ng· mL-1 · h-1;AUC0-∞ were (6841.98 ± 1975.95),(4656.66 ± 1083.78) and (4736.47 ± 897.42) ng · mL-1 · h;Cmax were (858.65 ± 275.98),648.81 ± 215.59) and (617.49 ± 168.95)ng · mL-1;t1/2 were (6.40 ± 2.18),(5.25 ± 1.39) and (5.68 ± 2.08) h;tmax were (0.88 ± 0.23),(0.90 ± 0.21) and (1.30 ± 0.59) h;clearance (CL) were (2.82±0.72) (4.07±0.99) and (3.95±0.91) L·h-1 ·kg-1;apparent volume of distribution (Ⅴ) were (26.07 ± 12.00),(31.45 ± 14.65) and (32.95 ± 14.17) L · kg-1.There were significant differences in AUC0-t,AUC0-∞,Cmax,tmax and CL between test A group and control group (P ＜ 0.05).On the contrary,no significant differences were observed on the pharmacokinetic parameters between test B group and control group.Conclusion Increased intestinal probiotics can increase the AUC0-t,AUC0-∞,and Cmax of ticagrelor,while decrease the CL of ticagrelor.关键词
替格瑞洛/高效液相色谱-串联质谱/肠道菌群/药代动力学Key words
ticagrelor/LC-MS/MS/intestinal flora/pharmacokinetics分类
医药卫生引用本文复制引用
苏子云,袁叶,李浩然,彭怡,杨秀岭..肠道菌群变化对替格瑞洛在大鼠体内药代动力学的影响[J].中国临床药理学杂志,2017,33(7):602-604,608,4.基金项目
河北省科技计划基金资助项目(14277767D) （14277767D）
