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Study on the effect of multiple drugs on P-glycoprotein in ileum of rats |
YUAN Jian, WAN Jun |
Department of Gastroenterology, the Second Medical Center, Chinese PLA General Hospital, Beijing 100853,China |
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Abstract 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 .
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Received: 20 June 2020
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