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目的:研究纤溶化合物FGFC1在Caco-2细胞模型中的吸收和转运特性。方法:以跨膜电阻值(transepithelial electrical resistance,TEER)值、阳性对照药荧光黄和普萘洛尔的表观渗透系数(the apparent permeability coefficients,Papp)值来评价模型的完整性、紧密性和通透性。通过LC/MS/MS考察浓度为0.5~5μmol·L-1的FGFC1溶液所产生的外排比、总回收率和表观渗透系数来评价药物的转运特性。结果:本实验培养的Caco-2细胞显示出优良的完整性、紧密性和通透性。在AP→BL方向的总回收率是(35.778±1.285)%~(52.336±4.342)%,在BL→AP方向的总回收率是(25.485±1.131)%~(53.022±2.011)%,AP→BL方向和BL→AP方向的Papp值均小于2.5×10-6cm·s-1,在AP→BL方向的外排比率是(8.745±0.155)%~(26.759±1.024)%,在BL→AP方向的外排比率是(25.549±1.551)%~(52.421±2.203)%。结论:FGFC1不是P-gp的底物。0.1%BSA能明显提高回收率和改善特异性吸附。FGFC1在Caco-2细胞模型中以被动扩散为主。FGFC1低渗透率的研究结论显示出静脉注射给药途径较口服给药途径更为恰当。
OBJECTIVE: To study the absorption and transport of fibrinolytic compound FGFC1 in Caco-2 cell model. Methods: The integrity, tightness and permeability of the model were evaluated by the values of transepithelial electrical resistance (TEER), positive control fluorescent yellow and propofol’s apparent permeability coefficients (Papp) Sex. The efflux ratio, total recovery and apparent permeability coefficient of FGFC1 solution with 0.5 ~ 5μmol·L-1 concentration were investigated by LC / MS / MS to evaluate the drug transport properties. Results: Caco-2 cells cultured in this experiment showed excellent integrity, tightness and permeability. The total recovery in the direction of AP → BL was (35.778 ± 1.285)% ~ (52.336 ± 4.342)%, and the total recovery in the direction of BL → AP was (25.485 ± 1.131)% ~ (53.022 ± 2.011)%. Papp values in both BL and BL → AP directions were less than 2.5 × 10-6cm · s-1, and the ratio of efflux in the AP → BL direction was (8.745 ± 0.155)% ~ (26.759 ± 1.024)%. The rate of efflux was (25.549 ± 1.551)% ~ (52.421 ± 2.203)%. Conclusion: FGFC1 is not a substrate of P-gp. 0.1% BSA can significantly improve the recovery rate and improve the specific adsorption. FGFC1 is mainly passive diffusion in Caco-2 cell model. The conclusions of FGFC1’s low permeability study show that intravenous route of administration is more appropriate than oral route.