艾司奥美拉唑对柳氮磺吡啶在大鼠体内药动学行为的影响  

Effects of Esomeprazole on Pharmacokinetic Behavior of Sulfasalazine in Rats

作　　者：贾茹[1,2] 魏世杰 张文萍[1,3] 买淑霞[1] 蒋韶婓 党宏万 JIA Ru;WEI Shijie;ZHANG Wenping;MAI Shuxia;JIANG Shaofei;DANG Hongwan(Dept.of Pharmacy,General Hospital of Ningxia Medical University,Yinchuan 750004,China;College of Pharmacy,Ningxia Medical University,Yinchuan 750004,China;Institute of Clinical Pharmacology,General Hospital of Ningxia Medical Universtiy,Yinchuan 750004,China;Dept.of Pharmacy,Qingdao Jiaozhou Central Hospital,Shandong Qingdao 266300,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临床药理研究室,银川750004 [4]青岛胶州中心医院药剂科,山东青岛266300

出　　处：《中国药房》2021年第13期1596-1601,共6页China Pharmacy

摘　　要：目的:建立测定大鼠血浆中柳氮磺吡啶(SSZ)代谢产物磺胺吡啶(SP)浓度的方法,并探讨艾司奥美拉唑(ESOM)对SSZ在大鼠体内药动学行为的影响。方法:将雄性SD大鼠随机分为SSZ组和SSZ+ESOM组,每组6只。SSZ+ESOM组大鼠连续灌胃艾司奥美拉唑肠溶片[90 mg/(kg·d)]14天;第15天时,两组大鼠单次灌胃柳氮磺吡啶肠溶片(90 mg/kg),并在给药后0.5、1、1.5、2、3、4、6、8、10、12、24、36、48、72 h时于其眼内眦取血。血浆经甲醇沉淀蛋白后,以地西泮为内标,以Agilent XDR-C18为色谱柱,以甲醇-0.1%甲酸溶液(梯度洗脱)为流动相,采用液相色谱-串联质谱法检测血浆中SSZ代谢产物SP的浓度;采用DAS 3.0.1软件计算药动学参数并进行组间比较。结果:SP检测质量浓度的线性范围为2~1000 ng/mL,方法学考察结果符合《中国药典》相应要求。SSZ+ESOM组和SSZ组大鼠体内SP的AUC_(0-t)、tmax、t_(1/2z)、cmax、MRT_(0-t)等药动学参数比较,差异均无统计学意义(P>0.05)。结论:所建方法简便、快速、灵敏度高,可用于血浆中SSZ代谢产物SP浓度的检测;ESOM对SSZ在大鼠体内的药动学行为无明显影响。OBJECTIVE:To develop a method for determining the plasma concentration of sulfasalazine(SSZ)metabolite sulfapyridine(SP)in rats,and to investigate the effects of esomeprazole(ESOM)on the pharmacokinetic behavior of SSZ in rats.METHODS:Male SD rats were randomly divided into SSZ group and SSZ+ESOM group,with 6 rats in each group.SSZ+ESOM group were given Esomeprazole enteric-coated tablets[90 mg/(kg·d)]intragastrically for 14 days.On the 15th day,the rats in 2groups were given Sulfasalazine enteric coated tablets(90 mg/kg)intragastrically,and blood sample was collected from the inner canthus at 0.5,1,1.5,2,3,4,6,8,10,12,24,36,48,72 h after administration.After protein precipitation with methanol,using diazepam as internal standard,Agilent XDR-C18column was adopted with methanol-0.1%formic acid solution(gradient elution)as mobile phase.The concentration of SSZ metabolite SP in plasma was determined by LC-MS/MS.The pharmacokinetic parameters were calculated by using DAS 3.0.1 software and compared between 2 groups.RESULTS:The linear range of SP were2-1000 ng/mL.The methodology met the requirements of Chinese Pharmacopeia.There was no statistical significance in pharmacokinetic parameters of SP between 2 groups,such as AUC_(0-t),tmax,t_(1/2z),cmax,MRT_(0-t)(P>0.05).CONCLUSIONS:The established method is simple,rapid and sensitive;it can be used for the concentration determination of SSZ metabolite SP in plasma.ESOM has no significant effect on the pharmacokinetic behavior of SSZ in rats.

关 键 词：柳氮磺吡啶 磺胺吡啶 艾司奥美拉唑 液相色谱-串联质谱法 药动学行为 

分 类 号：R969.1[医药卫生—药理学]