食物对艾司奥美拉唑镁、泮托拉唑钠和雷贝拉唑钠的药动学影响

Effect of food on the pharmacokinetics of esomeprazole magnesium, pantoprazole sodium, and rabeprazole sodium

目的:基于质子泵抑制剂(proton pump inhibitors,PPIs)类药物的生物等效性试验,探讨不同给药条件下药动学参数的变化规律,为临床合理用药提供依据。方法:217例中国健康志愿者在空腹或进食条件下单剂量口服PPIs类药物(艾司奥美拉唑镁肠溶胶囊40 mg、泮托拉唑钠肠溶片40 mg或雷贝拉唑钠肠溶片10 mg),根据方案要求采集静脉血样,用超高效液相色谱-串联质谱(UPLC-MS/MS)法分别测定人血浆中PPIs类药物的浓度,Phoenix WinNonlin 8.2统计软件计算药动学参数。结果:餐后给药艾司奥美拉唑镁T_(max)显著增加,C_(max)和AUC降低;泮托拉唑钠T_(max)增加,AUC降低;雷贝拉唑钠T_(max)、C_(max)和AUC均增加。结论:食物延迟PPIs类药物的吸收,影响生物利用度,临床适宜空腹给药。

OBJECTIVE This study is based on the bioequivalence test of proton pump inhibitors(PPIs),to explore the changing law of pharmacokinetic parameters under different conditions of drug administration,and to provide a basis for the rational use of drugs in the clinic.METHODS 217 healthy Chinese volunteers were given single-dose oral administration of PPIs analogues(esomeprazole magnesium enteric capsules 40 mg,pantoprazole sodium enteric tablets 40 mg,or rabeprazole sodium enteric tablets 10 mg)under fasting or eating conditions,and venous blood samples were collected according to the protocol requirements,and the concentrations of PPIs analogues in human plasma were determined by the UPLC-MS/MS method,respectively,and Phoenix WinNonlin 8.2 statistical software was used to calculate pharmacokinetic parameters.RESULTS Postprandial administration of esomeprazole magnesium was associated with a significant increase in T_(max) and a decrease in C_(max) and AUC;pantoprazole sodium was associated with an increase in T_(max) and a decrease in AUC;and rabeprazole sodium was associated with an increase in T_(max),C_(max) and AUC.CONCLUSION Food delays the absorption of PPIs and affects bioavailability,and is clinically appropriate for administration on an empty stomach.