摘要
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 investigate the pharmacokinetic interactions after oral administration of mosapride citrate, omeprazole and hydrochloride fluoxetine in treatment of rats with functional dyspesia. Methods Four groups of male SD rats（ Ⅰ , Ⅱ , Ⅲ, Ⅳ, n = 6 per group） were set in parallel design,the rats were given mosapride citrate,omeprazole,fluoxetine and combination of the three single doses ,by intragastric administration. The determination of plasma samples were performed by a HPLC-MS/MS and the pharmacokinetie parameters were estimated （ DAS 2.0）. Results The Cmax and AUC of mosapride citrate, as well as ome- prazole,were significantly increased;the AUC of hydroehlorid fluoxetine were increased, and CL/F of mosapride citrate, ome- prazole and hydrochloride fluoxetine was decreased. Conclusion The results of preliminary study showed that there were obvious pharmaeokinetic interactions among mosapride citrate, omeprazole and hydrochloride fluoxetine. The dosage of the three drugs was suggested to be reduced appropriately in their combination therapy.
出处
《中华全科医学》
2012年第11期1665-1667,共3页
Chinese Journal of General Practice
