DOI: 10.5176/2345-783X_PHARMA13.08
Authors: Ranjeet Prasad Dash, Bhanuchander Ellendula and Manish Nivsarkar
Abstract:
Type II diabetes is one of the most prevalent metabolic syndrome which on progression leads to many complications viz. obesity, insulin resistance, hypertension, dyslipidemia etc. Although various physiological mechanisms may be attributed for the development and progression of this disorder, increased oxidative stress is considered as one of the primary cause for the advancement of this disease. One of the major associated complication that results from this high oxidative stress, is the over expression of P-glycoprotein (P-gp), which is an important drug efflux transporter in different body tissues. Generally, P-gp is concerned for effluxing xenobiotics out of the cell, but in the mean time the drugs which are its substrates are also effluxed out of the system in normal physiological conditions, which subsequently results in decreased bioavailability. In diabetes, an overexpression of P-gp may be expected subsequently resulting in decreased bioavailability and efficacy of the drugs. Based on this hypothesis, we tried to determine the intestinal absorption of P-gp substrate (verapamil) in type II diabetes in rats using in situ intestinal perfusion technique. Moreover, we also made an attempt to check the extent of drug absorption with disease progression in different intestinal segments (duodenum, jejunum and ileum). Another aspect of our study was to evaluate the influence of epigallocatechin-3-gallate (EGCG), a P-gp inhibitor on intestinal uptake of verapamil. The results of this study inferred reduced intestinal absorption of verapamil in diabetic animals as compared to normal rats (p≤0.05) and intestinal absorption of verapamil also decreased with progression of diabetes. We also found that EGCG significantly improved the intestinal absorption of verapamil in a dose dependent manner. Thus it may be concluded that temporary inhibition of P-gp may serve as a potential approach for improving the oral bioavailability of P-gp substrate. However, the risk-benefit ratio for the same has to be evaluated.
Keywords: Diabetes, P-glycoprotein, Epigallocatechin-3-gallate, Verapamil
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