Polymeric and low molecular mass efflux pump inhibitors for oral drug delivery.

Transmembrane located transporter proteins can be responsible for the low bioavailability of orally administered drugs. Drug delivery systems which can overcome this barrier caused by efflux pumps are therefore highly on demand. Within the current review, intestinal located efflux transporters, methods to identify efflux pump substrates and inhibitors as well as strategies to minimize efflux pump mediated transport of drugs are discussed. Methods include in silico screening, transport and accumulation studies and monitoring of the ATPase activity. An emphasis has been placed on efflux pump inhibitors including low molecular mass inhibitors such as cyclosporine, PSC833 or KR30031 and polymeric inhibitors such as myrj, thiomers and cremophor EL. Also formulation approaches to circumvent intestinal segments with high efflux pump expression are briefly addressed. (c) 2007 Wiley-Liss, Inc.