Abstract

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 formulation development.

Keywords: ATP-Binding cassette family, bioavailability, cytochromep450, oral drug delivery, P-gp efflux pump, P-gp inhibitors, transporters.