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目的:比较丹酚酸B(SAB)和丹酚酸B二甲酯(DMB)在Caco-2细胞模型中的转运特性及影响因素。方法:以Caco-2细胞作为吸收研究模型,分别考察药物浓度、顶侧p H及外排蛋白抑制剂对SAB和DMB转运的影响,采用HPLC-MS/MS法检测药物浓度,计算并对比两者的表观渗透系数(P_(app))、外排比及总回收率。结果:在相同浓度下,SAB和DMB的A-to-B转运的P_(app)无明显差异,而B-to-A转运的P_(app)和外排比在高浓度下有显著性差异(P<0.05),且DMB的P_(app)和外排比明显比SAB高;顶侧p H的改变对两者的转运结果没有显著影响;而外排蛋白P-gp和BCRP对DMB的外排作用要强于SAB。结论:SAB和DMB均为低渗透性化合物,可能不是外排蛋白P-gp和BCRP的底物或是弱的底物,SAB的二甲基酯化并没有改变其渗透性。
OBJECTIVE: To compare the transport characteristics and influencing factors of salvianolic acid B (SAB) and salvianolic acid B dimethyl ester (DMB) in Caco-2 cell model. METHODS: Caco-2 cells were used as absorption models to investigate the influence of drug concentration, top p H and efflux inhibitor on the transport of SAB and DMB. HPLC-MS / MS was used to determine the drug concentration. The apparent permeability coefficient (P_ (app)), efflux ratio and total recovery. Results: There was no significant difference in A-to-B transport P app between SAB and DMB at the same concentration, while there was a significant difference between P-app and efflux ratio of B-to-A transport at high concentration P <0.05), and the P app ratio and efflux ratio of DMB were significantly higher than those of SAB. The changes of p H on the top side had no significant effect on the translocation of the two. However, the efflux of P-gp and BCRP on the efflux of DMB The effect is stronger than SAB. Conclusion: Both SAB and DMB are low permeability compounds and may not be substrates or weak substrates for efflux proteins P-gp and BCRP. Dimethyl esterification of SAB did not change its permeability.