目的 评价共病治疗中多药同服对大鼠回肠黏膜P糖蛋白的影响。方法 选择Wistar雌性大鼠(北京维通利华)40只,8周龄,(230±20) g,随机分为4组(n=10)。单药组给予氯吡格雷,多药组给予氯吡格雷、雷贝拉唑、草酸艾司西酞普兰、甲苯磺丁脲,阳性对照组给予维拉帕米,空白对照组给予生理盐水,各实验组灌胃1周后使用体外垂直型扩散池技术(ussing chamber),评价罗丹明123(Rhodamine123,R123)和荧光素钠(fluorescein sodium,CF)经大鼠回肠黏膜的经时吸收方向和分泌方向的累计透过量和表观渗透系数。R123和CF在接受室的浓度用荧光分光光度计检测。结果 阳性对照组与空白对照组相比,透过率有显著增加趋势,差异有统计学意义(P＜0.05)。R123经大鼠回肠黏膜分泌方向的经时曲线,多药组和单药组相比,透过率显著增高,差异有统计学意义(P＜0.05)。CF经大鼠回肠吸收和分泌的经时累计透过率和Papp,除了空白对照组使CF在吸收方向和分泌方向透过增加,其余药物均使CF的透过显著降低。结论 氯吡格雷可以抑制回肠P-gp的功能,但是多药同时服用会明显减弱氯吡格雷的这种抑制作用。因此,在共病治疗或者综合性治疗时,尽量避免多种药物同时服用,防止出现口服药物生物利用度降低。

Objective To evaluate the effects of multiple drugs in the treatment of comorbidities on P glycoprotein in the ileal mucosa of rats.Methods Forty female Wistar rats (Beijing Weitonglihua), 8 weeks old, (230±20) g, were selected and randomly divided into 4 groups (n=10). The single-drug group was given clopidogrel, the multi-drug group was given clopidogrel, rabeprazole, escitalopram oxalate, and tolbutamide, the positive control group was given verapamil, and the blank control group was given normal saline. The experimental group used the vertical diffusion cell technique (ussing chamber) after intragastric administration for one week to evaluate the accumulation of Rhodamine 123(Rhodamine 123 R123) and fluorescein sodium (fluorescein sodium CF) through the ileal mucosa of the rat in the direction of absorption and secretion over time. Permeability and apparent permeability coefficient. The concentration of R123 and CF in the receiving chamber was detected with a fluorescence spectrophotometer.Results Compared with the blank control group, the transmittance of the positive control group had a significant increasing trend, and the difference was statistically significant (P＜0.05). The time-dependent curve of the direction of R123 secretion through the ileal mucosa of rats. Compared with the single-drug group, the transmission rate of the multi-drug group was significantly higher, and the difference was statistically significant (P＜0.05). The cumulative permeation rate and Papp of CF absorbed and secreted through the rat ileum over time. Except for the blank control group, which increased the permeation of CF in the direction of absorption and secretion, the other drugs significantly reduced the permeation of CF.Conclusions Clopidogrel can inhibit the function of P-gp in the ileum, but taking multiple drugs at the same time will significantly weaken the inhibitory effect of clopidogrel. Therefore, in the treatment of comorbidities or comprehensive treatment, try to avoid taking multiple drugs at the same time to prevent the decrease in the bioavailability of oral drugs .