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 .
苑键, 万军. 多药同服对大鼠回肠P-糖蛋白的影响[J]. 武警医学, 2021, 32(5): 369-372.
YUAN Jian, WAN Jun. Study on the effect of multiple drugs on P-glycoprotein in ileum of rats. Med. J. Chin. Peop. Armed Poli. Forc., 2021, 32(5): 369-372.
Masnoon N, Shakib S, Kalisch-Ellett L, et al. What is polypharmacy？ A systematic review of definitions[J]. BMC Geriatr, 2017,17(1):230-241.
[2]
Rocco N, Rispoli C, Pagano G, et al. Retraction note: undertreatment of breast cancer in the elderly [J]. BMC Surg, 2016,16(1):25-26.
[3]
van Waart H, Stuiver M M, van Harten W H, et al. Recruitment to and pilot results of the PACES randomized trial of physical exercise during adjuvant chemotherapy for colon cancer[J]. Int J Colorectal Dis, 2018, 33(1): 29-41.
[4]
Li J, Liu Y, Zhang J, et al. Effects of resveratrol on P-glycoprotein and cytochrome P450 3A in vitro and on pharmacokinetics of oral saquinavir in rats[J]. Drug Des Devel Ther, 2016, 10: 3699-3706.
[5]
Freitas E D, Moura C F Jr, Kerwald J, et al. An Overview of current knowledge on the properties, synthesis and applications of quaternary chitosan derivatives [J]. Polymers (Basel), 2020,12(12) :2878-2910.
[6]
Golfar Y, Shayanfar A. Prediction of biopharmaceutical drug disposition classification system (BDDCS) by structural parameters[J]. J Pharm Pharm Sci, 2019, 22(1):247-261.
[7]
Akazawa T, Yoshida S, Ohnishi S, et al. Application of intestinal epithelial cells differentiated from human induced pluripotent stem cells for ctudies of prodrug hydrolysis and drug absorption in the small intestine[J]. Drug Metab Dispos, 2018,46(11):1497-1547.
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