艾司奥美拉唑对对乙酰氨基酚药动学与肠道菌群的影响  

Effct of Esomeprazole on Acetaminophen Pharmacokinetics and Intestinal Microbial Balance

作　　者：贾茹[1] 王怡帆 陈文华[1] 张文萍[3] 贺少龙 党宏万[1] 魏世杰[1] JIA Ru;WANG Yifan;CHEN Wenhua;ZHANG Wenping;HE Shaolong;DANG Hongwan;WEI Shijie(Department of Pharmacy,General Hospital of Ningxia Medical University,Yinchuan 750004,China;School of Pharmacy,Ningxia Medical University,Yinchuan 750004,China;Institutional Office of Drug Clinical Trial,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学总医院药剂科,银川750004 [2]宁夏医科大学药学院,银川750004 [3]宁夏医科大学总医院药物临床试验机构办公室,银川750004

出　　处：《医药导报》2024年第6期862-866,共5页Herald of Medicine

基　　金：宁夏自然科学基金重点研发计划项目(2021BEG03102)。

摘　　要：目的探讨质子泵抑制剂(PPI)艾司奥美拉唑(EMZ)对对乙酰氨基酚(APAP)药动学与肠道菌群生态平衡的作用。方法将14只SD大鼠随机分为2组,分别为APAP组、APAP+EMZ组,每组7只;将APAP+EMZ组大鼠置于代谢笼中饲养。APAP+EMZ组灌胃给予EMZ 3.6 mg·kg^(-1)·d^(-1),APAP组以等体积0.9%氯化钠溶液代替,连续灌胃14 d;分别在给予EMZ前和给药14 d后收集大鼠粪便进行微生物16SrRNA测序。第15天APAP组和APAP+EMZ组灌胃EMZ后同法给予APAP 44.82 mg·kg^(-1)。超高效液相色谱-串联质谱(UPLC-MS/MS)法测定样品中APAP浓度。计算药动学参数并统计分析,比较APAP组和APAP+EMZ组APAP药动学参数。结果①两组APAP的达峰浓度(C max)比较差异有统计学意义(P<0.05),与APAP组比较,APAP+EMZ组C max增加120.38%。两组血药浓度-时间曲线下面积(AUC_((0-∞)))、清除率(CL)、消除半衰期(t_(1/2))和达峰时间(t_(max))比较均差异无统计学意义(均P>0.05);②使用EMZ后乳酸杆菌属、拟杆菌属、梭状芽孢杆菌属和埃希杆菌属相对丰度较用药前减少,而双歧杆菌属增加。但上述菌群相对丰度在EMZ干预前后差异无统计学意义(P>0.05)。结论EMZ与APAP联用时,影响β-葡萄糖醛酸苷酶的菌群相对丰度有一些变化,EMZ对APAP的C_(max)有影响;使用EMZ 2周不通过影响肠道菌群而改变APAP的药动学。Objective To explore esomeprazole(EMZ)on acetaminophen(APAP)pharmacokinetics and intestinal microbial balance.Methods A total of 14 rats were randomly allocated into two groups,with 7 rats in each group:acetaminophen group(APAP group),and acetaminophen+esomeprazole combination group(APAP+EMZ group),respectively.Rats in the combination group were fed in the metabolic cage.Equivalent 3.6 mg·kg^(-1)·d^(-1) esomeprazole was administered intragastrically to the combination group for 14 days;Similarly,an equal volume of 0.9%sodium chloride soution(NaCl)was fed to the APAP group for 14 days.During this period,fecal samples were collected from the rats before and after 14 days of EMZ administration for microbial 16S rRNA sequencing.On the 15th day,both the APAP group and APAP+EMZ groups were administratered an equivalent of 44.82 mg·kg^(-1) APAP by the same method after the regular EMZ administration.The concentrations of APAP in rat plasma were determined by the UPLC-MS/MS method.Main pharmacokinetic parameters were processed and compared using the software DAS 3.0.1 and SPSS 24.0.Results The pharmacokinetic parameter C max of APAP was significantly different between APAP group and APAP+EMZ group(P<0.05).Compared with APAP group,C max increased by 120.38%in the APAP+EMZ group.The pharmacokinetic parameters(AUC_((0-∞))、CL、t_(1/2)、t_(max))of APAP showed no statistical differences between APAP group and APAP+EMZ group(P>0.05).The results of 16SrRNA of intestinal flora showed that the abundance of Lactobacillus,Bacteroides,Clostridium,and Escherichia decreased compared with that before drug administration,while the abundance of Bifidobacterium increased.However,the relative abundance of the above flora showed no prominent differences before and after the EMZ intervention(P>0.05).Conclusions This study showed that when combining EMZ with APAP,the relative abundance of those related flora,which may influence theβ-Glucuronidase,all changed to some extent,but made no difference in statistics.The effect of EMZ on the

关 键 词：对乙酰氨基酚 艾司奥美拉唑 超高效液相色谱-串联质谱 药动学 肠道菌群 

分 类 号：R969.2[医药卫生—药理学]