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恩替卡韦(ETV)是一线抗乙肝病毒(HBV)药物,黄芪汤(HQD)临床上对肝硬化有改善效应,两者可合用治疗乙肝肝硬化患者。本文建立了超高效液相色谱-线性离子阱-静电场轨道阱组合质谱法(UHPLC-LTQOrbitrap)测定大鼠血浆中恩替卡韦浓度,方法学考察表明恩替卡韦在0.100~20.0 ng·m L-1浓度内线性关系良好,符合生物样本测定要求。SD大鼠随机分成6组,有单次、多次给药,再分别分为单用恩替卡韦组(ETV组)、恩替卡韦与黄芪汤同时给药组(ETV-HQD组)和灌服恩替卡韦2 h后再给药黄芪汤组(ETV-HQD-2h组),采用建立的UHPLC-LTQ-Orbitrap法测定恩替卡韦浓度。与ETV组相比,ETV-HQD组中恩替卡韦C_(max)降低,t_(max)延长,AUC0–t减少。ETV-HQD-2h组中黄芪汤与恩替卡韦间隔2 h给药对恩替卡韦药动学行为无显著影响。外翻肠囊实验发现,黄芪汤阻碍了恩替卡韦在小肠黏膜表面的吸收。结果表明,黄芪汤与恩替卡韦同时给药可减少恩替卡韦的吸收。
Entecavir (ETV) is a first-line anti-hepatitis B virus (HBV) drug, and Astragalus soup (HQD) has an improved clinical effect on cirrhosis. Both of them can be used in the treatment of hepatitis B cirrhosis patients. In this paper, UHPLC-LTQOrbitrap was used to determine the concentration of entecavir in rat plasma. The methodological study showed that entecavir concentration in the range of 0.100-20.0 ng · m L-1 Linear relationship is good, in line with the biological sample determination requirements. SD rats were randomly divided into 6 groups: single-dose and multiple-dose. ETV-HQD group and ETV-HQD group were enrolled in the study. Administration of Astragalus soup group (ETV-HQD-2h group), and determination of entecavir concentration by established UHPLC-LTQ-Orbitrap method. Compared with ETV group, Cmax of entecavir in ETV-HQD group was decreased, t max was prolonged and AUC0-t was decreased. ETV-HQD-2h group Astragalus soup and entecavir interval 2 h administration of entecavir pharmacokinetics had no significant effect. Valgus capsule experiment found that Astragalus soup hinder the absorption of entecavir in the intestinal mucosal surface. The results show that the simultaneous administration of Astragalus soup and entecavir can reduce the absorption of entecavir.