Membrane transporters

Carrier-mediated drug transport is relatively unexplored in comparison with passive transcellular and paracellular drug transport. Yet, there is a hos t of transporter proteins that can be targeted for improving epithelial dru g absorption. Generally, these are transport mechanisms for amino acids, di peptides, monosaccharides, monocarboxylic acids, organic cations, phosphate s, nucleosides, and water-soluble vitamins. Among them, the dipeptide trans porter mechanism has received the most attention. Dipeptide transporters ar e H+-coupled, energy-dependent transporters that are known to play an essen tial role in the oral absorption of beta -lactam antibiotics, an,angiotensi n-converting enzyme (ACE) inhibitors, renin inhibitors, and an anti-tumor d rug, bestatin. Moreover, several investigators have demonstrated the utilit y of the dipeptide transporter as a platform for improving the oral bioavai lability of drugs such as zidovudine and acyclovir through dipeptide prodru g derivatization. Thus far, at least four proton-coupled peptide transporte rs have been cloned. The first one cloned was PepT1 from the rabbit small i ntestine. The focus of this presentation will be structure-function, intrac ellular trafficking, and regulation of PepT1. Disease, dietary, and possibl e excipient influences on PepT1 function will also be discussed. (C) 2000 E lsevier Science B.V. All rights reserved.