Drug molecule has to overcome numerous encounters after oral administration and before it reaches to the site
of action. The topmost hindrances to drug after oral administration comprise of degradation by enzymes, corporal fence of
the intestinal epithelial membrane, biliary excretion and active efflux back into the lumen of the gastrointestinal tract.
Nowadays with hurried advances in drug design technologies, druggable compounds have dramatically been introduced.
However, several of these molecules have suffered from low bioavailability upon oral administration due to poor
permeation across the gastrointestinal epithelia although they exhibit potential therapeutic effects. This issue of poor
membrane permeability is mainly due to the transporter proteins present in the membrane. ATP binding cassette [ABC]
super family acts as a carrier mediated active efflux transporter. In this family P-glycoprotein [P- gp], MRP1 and ABCG2
are most known multidrug efflux pumps. Amongst all the three efflux transporters, P-gp is extensively distributed in the
human body and has enormous variety of substrates specificity for many drugs. Many therapeutically potential drugs have
low bioavailability due to P-gp efflux. Therefore, to overcome multidrug resistance and deprived bioavailability of P-gp
substrates, P-gp inhibitors have been discovered. The main aim of this review is to underline challenges in oral drug
delivery, specifically focusing on P-gp efflux and contemporary strategies used for P-gp inhibition in drug discovery and
Keywords: ATP-Binding cassette family, bioavailability, cytochromep450, oral drug delivery, P-gp efflux pump, P-gp
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