高脂高热量饮食对中国健康受试者口服雷贝拉唑钠肠溶片药代动力学的影响  

Effects of high-fat diet intake on pharmacokinetics of rabeprazole sodium enteric-coated tablets in healthy Chinese subjects

作　　者：郭彩会[1] 许玉芳[1] 丁琮洋 郝光涛 宋浩静[1] 孙雪 董占军[1] 白万军[1] GUO Cai-hui;XU Yu-fang;DING Cong-yang;HAO Cuang-tao;SONG Hao-jing;SUN Xue;DONG Zhan-jun;BAI Wan-jun(Department of Pharmacy,Hebei Key Laboratory of Clinical Pharmacy,Hebei General Hospital,Shijiazhuang 050051,Hebei Province,China;Bejing Scinovo Laboratories Ltd,Beijing 110105,China)

机构地区：[1]河北省人民医院药学部河北省临床药学重点实验室,河北石家庄050051 [2]北京阳光德美医药科技有限公司,北京110105

出　　处：《中国临床药理学杂志》2025年第2期225-229,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的观察中国健康受试者空腹和高脂高热量饮食情况下口服雷贝拉唑钠肠溶片的药代动力学特征。方法用单中心、随机、开放、两制剂、两序列、四周期、完全重复交叉、单次给药试验设计。健康受试者分别在空腹或高脂高热量饮食条件下单剂量口服雷贝拉唑钠肠溶片0.1g,分别按方案规定的时间点采集静脉血样,用液相色谱-串联质谱(LC-MS/MS)法测定人血浆中雷贝拉唑的血药浓度,用Phoenix WinNonlin8.2软件按非房室模型法计算药代动力学参数。结果雷贝拉唑钠肠溶片空腹和高脂高热量饮食后的主要药代动力学参数:Cmax分别为(339.63±156.47)和(318.86±132.13)ng·mL(-1),t_(1/2)分别为(2.34±0.68)和(3.60±2.40)h,AUC_(0-t)分别为(556.62±251.65)和(528.50±201.78)ng·mL(-1)·h,AUC_(0-∞)分别为(563.39±255.69)和(535.15±203.24)ng·mL^(-1)·h,t_(max)分别为3.65和6.99h。高脂高热量饮食后服药与空腹条件下服药相比,雷贝拉唑钠C_(max)和AUC均降低,C_(max)降低6.12%,AUC(0-t)降低5.05%,AUC_(0-∞)降低5.01%,t_(max)延迟约3.34h。C_(max)、AUC_(0-t)、AUC_(0-∞)90%置信区间分别为73.13%~115.10%、83.22%~112.28%、83.40%~112.13%,均不在85.00%~125.00%内。结论高脂高热量饮食影响雷贝拉唑钠肠溶片的吸收速度和吸收程度,临床适宜空腹给药。Objective To evaluate the effects of fasting and high-fat diet on the pharmacokinetics of rabeprazole sodium enteric-coated tablets in healthy Chinese subjects.Methods A single-center,randomized,open,two-agent,two-sequence,four-cycle,fully repeated crossover,single-dose trial design was used in this study,healthy subjects were assigned to receive single dose of rabeprazole sodium enteric-coated tablets 0.1 g in either fasting or high-fat diet state,and blood samples were taken at different time points,respectively.The concentrations of rabeprazole sodium enteric-coated in plasma were determined by liquid chromatography-tandem masssspectrometry(LC-MS/MS),the model method of the non-compartmental was used to calculate the pharmacokinetic parameters by Phoenix WinNonlin 8.2.Results The main pharmacokinetic parameters of rabeprazole sodium enteric-coated tablets in fasting state and high-fat diet state were as follows:C_(max)were(339.63±156.47)and(318.86±132.13)ng·mL^(-1);t_(1/2) were(2.34±0.68)and(3.60±2.40)h;AUC_(0-t)were(556.62±251.65)and(528.50±201.78)ng·mL^(-1).h;AUC_(0-∞)were(563.39±255.69)and(535.15±203.24)ng·mL^(-1)·h;t_(max)were 3.65 and 6.99 h.After high-fat diet,the C_(max)and AUC of rapeprazole sodium after high-fat and high-calorie diet decreased,C_(max)decreased by 6.12%,AUC_(0-t)decreased by 5.05%,AUC_(0-∞)decreased by 5.01%,and tmx was delayed by about 3.34 h.Cmax,AUC_(0-t)and AUC_(0-∞)confidence interval were 73.13%-115.10%,83.22%-112.28%and 83.40%-112.13%,respectively.Neither was between 85.00%-125.00%.Conclusion High-fat diet affects the absorption rate and degree of rabeprazole sodium enteric-coated,so it is suitable to be administered on an empty stomach.

关 键 词：雷贝拉唑钠肠溶片 高脂高热量饮食 药代动力学 食物效应 液相色谱-串联质谱法 

分 类 号：R975[医药卫生—药品]