摘要
目的:研究雷贝拉唑(RPZ)对大鼠体内氯吡格雷(CLP)抗血小板聚集作用和代谢的影响。方法:将40只SD大鼠随机分为空白对照组、RPZ组、CLP组、RPZ+CLP组、CLP+RPZ组,每组8只,CLP和RPZ的给药剂量分别为6.75、0.9 mg/kg,两药给药间隔2 h,连续给药14 d。检测各组大鼠血小板聚集率(MPA)、血小板活化指数(PRI)、胃黏膜损伤评分以及血药浓度[氯吡格雷羧酸(CA)及CLP活性巯基代谢物衍生物(AM)],并采用Pearson相关性分析法分析MPA和PRI分别与CA、AM的关系。结果:与空白对照组比较,CLP组、RPZ+CLP组和CLP+RPZ组大鼠的MPA、PRI均明显降低(P<0.05),胃黏膜损伤评分均明显增加(P<0.05),而RPZ组大鼠的MPA、PRI和胃黏膜损伤评分均无明显变化(P>0.05)。与CLP组比较,RPZ+CLP组和CLP+RPZ组大鼠的MPA、PRI均明显升高(P<0.05),胃黏膜损伤评分均明显减小(P<0.05),AM血药浓度明显降低(P<0.05),而3组大鼠的CA血药浓度无明显变化(P>0.05)。MPA和PRI均与AM呈负相关性(r=-0.689、-0.765,P<0.05),而与CA均未见明显的相关性(r=-0.117、0.048,P>0.05)。结论:RPZ对CLP的抗血小板作用、致胃黏膜损伤有一定的抑制作用,两药的给药顺序不影响CLP的代谢。
OBJECTIVE:To study the effects of rabeprazole(RPZ)on in vivo anti-platelet aggregation and metabolism of clopidogrel in rats.METHODS:Totally 40 SD rats were randomly divided into blank control group,RPZ group,CLP group,RPZ+CLP group and CLP+RPZ group,with 8 rats in each group.The dose of CLP and RPZ were 6.75 and 0.9 mg/kg,with medication interval of 2 h,for consecutive 14 d.The maximal platelet aggregation(MPA),platelet reaction index(PRI),gastric mucosal injury score and blood concentration[carboxylic acid of clopidogrel(CA)and active metabolite of clopidogrel(AM)were detected.The relationship of MPA and PRI with CA and AM were analyzed by Pearson relation analysis.RESULTS:Compared with blank control group,MPA and PRI of rats were decreased significantly in CLP group,RPZ+CLP group and CLP+RPZ group(P<0.05).Gastric mucosal injury score was increased significantly(P<0.05),while MPA,PRI and gastric mucosal injury score had no significant change in RPZ group(P>0.05).Compared with CLP group,MPA and PRI were increased significantly in RPZ+CLP group and CLP+RPZ group(P<0.05);gastric mucosal injury score was decreased significantly(P<0.05)and blood concentration of AM was also decreased significantly(P<0.05).Blood concentration of CA in 3 groups had no significant change(P>0.05).MPA and PRI were both negatively related with AM(r=-0.689,-0.765,P<0.05),while they had no significant correlation with CA(r=-0.117,0.048,P>0.05).CONCLUSIONS:RPZ can inhibit the antiplatelet effect of CLP and CLP-induced gastric mucosal injury,and medication order of two drugs doesn’t influence CLP metabolism.
作者
蔡薇薇
CAI Weiwei(Quality Control Department,General Hospital of Pingmeishenma Medical Group,Henan Pingdingshan 467000,China)
出处
《中国药房》
CAS
北大核心
2018年第17期2342-2346,共5页
China Pharmacy
基金
国家自然科学基金资助项目(No.81503005)
关键词
氯吡格雷
雷贝拉唑
抗血小板聚集
代谢
相互作用
大鼠
Clopidogrel
Rabeprazole
Anti-platelet aggregation
Metabolism
Drug-drug interaction
Rat
作者简介
蔡薇薇:副主任药师,硕士。研究方向:医院药学。电话:0375-2799566。E-mail:weiwei-pds@163.com
