Abstract
According to the recent advances in the molecular biological studies for biological membrane transport, a significant contribution of carrier-mediated transport mechanism in the intestinal absorption, tissue distribution, and renal and hepatic excretion for various drugs has been suggested. Oligopeptide transporter PepT1 is expressed at the brush-border membrane of intestinal epithelial cells and has a predominant role in intestinal absorption of natural di- and tripeptides. Interestingly PepT1 has broad substrate specificity and accepts various peptide mimetic drugs such as β-lactam antibiotics, angiotensin converting enzyme inhibitors, renin inhibitors and anticancer drug. Accordingly, PepT1 is expected to be used for improvement of intestinal absorption of poorly absorbed drugs by derivation of the drugs to peptide mimetics. When transport of L-phenylalanyl-peptide derivative (L-dopa-L-Phe) of L-dopa, an antiperkinsonian, across intestinal epithelial-like Caco-2 cells was measured, increased transport by utilization of PepT1 was demonstrated, suggesting an improvement of intestinal absorption by peptide-derivation strategy. Furthermore, the similar transport activity with PepT1 was demonstrated in certain tumor cells. Accordingly, delivery of peptide-mimetic anticancer drug to tumor by utilization of peptide transporter activity was also suggested. Since these physiological transporters are tissue and substrate specific, it is advantageous to improve pharmacokinetic features of drugs by utilization of these transporters.
