盐酸赛庚啶在Caco-2细胞中吸收转运的研究
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摘要
目的研究盐酸赛庚啶在Caco-2细胞模型中的吸收机制。方法建立Caco-2细胞体外吸收模型,通过测定荧光黄透过率、安替比林和普萘洛尔的渗透系数、地高辛的外排率验证Caco-2细胞吸收模型的成功建立。采用液相色谱-串联质谱(LC-MS/MS)法测定盐酸赛庚啶在膜两侧的浓度,计算渗透系数和外排率。结果 Caco-2模型建立成功,采用液相色谱-串联质谱法可以准确测定缓冲体系中盐酸赛庚啶的浓度。结论盐酸赛庚啶的渗透系数随药物浓度的变化而变化,且与转运方向有关,可能为P-糖蛋白(P-gp)和乳腺癌耐药蛋白(BCRP)的底物。
Objective To study the absorption mechanism of cyproheptadine hydrochloride in Caco-2 cell model.Methods In vitro drug absorption model of Caco-2 cells was established.To confirm Caco-2 cell model establishment was successful,the fluorescence yellow transmittance,the permeability coefficient of antipyrine and propranolol,and the efflux rate of digoxin were verified.The concentration of cyproheptadine hydrochloride on both sides of the membrane at different time points was determined by a LC-MS/MS method,and the permeability coefficient and efflux rate of the drug were calculated.Results The results of the fluorescence yellow transmittance indicated that Caco-2 cell model was successfully established.A LC-MS/MS method was established to accurately determine the concentration of cyproheptadine hydrochloride in the buffer system.Conclusion The permeability coefficient of cyproheptadine hydrochloride varied with different concentrations of the drug and was related to the transport direction.Furthermore,the efflux rate of the drug suggested that it may be a substrate for P-gp and BCRP.
Objective To study the absorption mechanism of cyproheptadine hydrochloride in Caco-2 cell model.Methods In vitro drug absorption model of Caco-2 cells was established.To confirm Caco-2 cell model establishment was successful,the fluorescence yellow transmittance,the permeability coefficient of antipyrine and propranolol,and the efflux rate of digoxin were verified.The concentration of cyproheptadine hydrochloride on both sides of the membrane at different time points was determined by a LC-MS/MS method,and the permeability coefficient and efflux rate of the drug were calculated.Results The results of the fluorescence yellow transmittance indicated that Caco-2 cell model was successfully established.A LC-MS/MS method was established to accurately determine the concentration of cyproheptadine hydrochloride in the buffer system.Conclusion The permeability coefficient of cyproheptadine hydrochloride varied with different concentrations of the drug and was related to the transport direction.Furthermore,the efflux rate of the drug suggested that it may be a substrate for P-gp and BCRP.
引文
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