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目的研究枸橼酸莫沙必利、奥美拉唑和盐酸氟西汀联合给药治疗大鼠功能性消化不良的药动学行为变化。方法 4组SD雄性大鼠分别为单药组枸橼酸莫沙必利(Ⅰ)、奥美拉唑(Ⅱ)、盐酸氟西汀(Ⅲ)和联合用药组(Ⅳ)。采用HPLC-MS/MS法同时测定大鼠给药后不同时间点的血药浓度(DAS 2.0程序拟合),估算药动学参数。结果枸橼酸莫沙必利、奥美拉唑与盐酸氟西汀均符合二室模型特征。三药合用时枸橼酸莫沙必利的Cmax和AUC显著增大,CL/F和V/F减小;奥美拉唑的Cmax和AUC显著增大,CL/F减小;盐酸氟西汀AUC增大,CL/F减小。结论枸橼酸莫沙必利、奥美拉唑和盐酸氟西汀联合应用时存在明显的药代动力学叠加作用,建议临床联合用药时适当减量。
Objective To study the pharmacokinetic behavior of mosapride citrate combined with omeprazole and fluoxetine hydrochloride in the treatment of functional dyspepsia in rats. Methods SD male rats were divided into two groups: mosapride citrate (Ⅰ), omeprazole (Ⅱ), fluoxetine hydrochloride (Ⅲ) and combination therapy group (Ⅳ). Pharmacokinetic parameters were estimated by HPLC-MS / MS simultaneous determination of plasma concentrations at different time points after administration in rats (DAS 2.0 program fitting). Results Mosapride citrate, omeprazole and fluoxetine hydrochloride all fit the two-compartment model. Cmax and AUC of mosapride citrate significantly increased and CL / F and V / F decreased when the three drugs were combined; the Cmax and AUC of omeprazole significantly increased and the CL / F decreased; Ting AUC increased, CL / F decreased. Conclusions Mosapride citrate, omeprazole and fluoxetine hydrochloride combined with significant pharmacokinetic additive effect, it is recommended that appropriate reduction of clinical combination therapy.