Abstract
Recently, it has been recognized that the intestinal transporters are the important factor for determining oral drug bioavailability. The efflux transporters in the intestine may limit drug absorption into the enterocyte thereby lowering the amount of drug available to enter the bloodstream. The oral administration of competing low molecular weight compounds, such as verapamil or cyclosporin can enhance the oral bioavailability of efflux transporter substrate drugs. Such competing compounds, however, have themselves pharmacological activity. So the challenge to find inhibitors of the efflux transporters that do not have such drawbacks is necessary.
It has been reported that excipients, which are commonly added to pharmaceutical formulations, may disrupt the function of intestinal efflux transporters and thus enhance the intestinal permeability of a substrate drug. Because inhibition of efflux transporters can have an effect on drug bioavailability, identification of these excipients and their extent of inhibition are therefore important for pharmaceutical development. In addition, understanding the detailed inhibition mechanism of the efflux transport system will contribute to the development of the optimized formulations that give higher oral bioavailability. This review focus on the possibility to improve oral bioavailability by inhibiting the function of efflux transporters, and their inhibition mechanism will be discussed.
