艾普拉唑肠溶片不同给药方案对其抑制胃酸分泌影响的研究  

Study on the effect of different administration regimens of iprrazole enteric-coated tablets on inhibiting gastric acid secretion

作　　者：庞廷媛 王芷 胡姊姝 申子涵 王悦琦 陈雅倩 钱学兵 梁锦莹 易良英 李俊龙 韩智慧 钟国平 程国华[3] 胡海棠[4] PANG Ting-yuan;WANG Zhi;HU Zi-shu;SHEN Zi-han;WANG Yue-qi;CHEN Ya-qian;QIAN Xue-bing;LIANG Jin-ying;YI Liang-ying;LI Jun-long;HAN Zhi-hui;ZHONG Guo-ping;CHENG Guo-hua;HU Hai-tang(Department of Pharmacy,Cancer Hospital Affiliated to Guangzhou Medical University,Guangzhou 510095,Guangdong Province,China;Clinical Trial Research Center of Dongguan Kanghua Hospital,Dongguan 523080,Guangdong Province,China;College of Pharmacy,Jinan University,Guangzhou 511400,Guangdong Province,China;Livzon Pharmaceutical Group Inc.,Zhuhai 519090,Guangdong Province,China;Institute of Clinical Pharmacology,Sun Yat-sen University,Guangzhou 510080,Guangdong Province,China)

机构地区：[1]广州医科大学附属肿瘤医院药学部,广东广州510095 [2]东莞康华医院临床试验研究中心,广东东莞523080 [3]暨南大学药学院,广东广州511400 [4]丽珠医药集团股份有限公司,广东珠海519090 [5]中山大学临床药理研究所,广东广州510080

出　　处：《中国临床药理学杂志》2024年第1期92-96,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的比较艾普拉唑肠溶片2种给药方案(20 mg qd和10 mg bid)对健康受试者的胃酸控制效果的影响。方法采用随机、单中心、平行对照试验设计,纳入8例健康受试者。随机分为2组,20 mg qd给药组:早上服用艾普拉唑肠溶片20 mg;10 mg bid给药组:早、晚各服用艾普拉唑肠溶片10 mg。用pH计监测受试者给药前及给药后24 h的胃内pH值,用液质联用技术(HPLC-MS/MS)测定受试者给药后血浆中的艾普拉唑浓度,用Phoenix WinNonlin(V8.0)软件计算主要药代动力学参数。结果空腹组的艾普拉唑肠溶片受试制剂和参比制剂主要PK参数:20 mg qd组和10 mg bid组Cmax分别为(595.75±131.15)和(283.50±96.98)ng·mL^(-1),AUC0-t分别为(5531.94±784.35)和(4686.67±898.23)h·ng·mL^(-1),AUC0-∞分别为(6003.19±538.59)和(7361.48±1816.77)h·ng·mL^(-1)。受试者接受20 mg qd与10 mg bid给药后胃内pH>3的平均时间百分比为82.64%及61.92%,24 h内胃pH中位数分别为6.25±1.49及3.53±2.05,24 h内胃pH平均数分别为5.71±1.36及4.23±1.45。同时药代动力学/药效学相关性分析表明,血浆中药物峰浓度与抑酸作用没有明显相关性。结论艾普拉唑20 mg qd与10 mg bid给药组相比,抑酸效果更优,给药次数少,且2种给药方案安全性均良好。Objective To compare the effects of 20 mg qd and 10 mg bid administration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL^(-1);AUC0-t were(5531.94±784.35)and(4686.67±898.23)h·ng·mL^(-1);AUC0-∞were(6003.19±538.59)and(7361.48±1816.77)h·ng·mL^(-1),respectively.The mean time percentage of gastric pH>3 after 20 mg qd and 10 mg bid were 82.64%and 61.92%,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

关 键 词：艾普拉唑 中国健康受试者 胃酸pH监测 药代动力学 

分 类 号：R97[医药卫生—药品]