Ps. Burton et al., IN-VITRO PERMEABILITY OF PEPTIDOMIMETIC DRUGS - THE ROLE OF POLARIZEDEFFLUX PATHWAYS AS ADDITIONAL BARRIERS TO ABSORPTION, Advanced drug delivery reviews, 23(1-3), 1997, pp. 143-156
Cellular efflux pathways function to remove both endogenous and exogen
ous substances from the cell. In the case of a polarized cellular barr
ier. such as the epithelium, these pathways serve an excretory or secr
etory role in transporting solutes out of tissue. Although well recogn
ized in organs typically associated with drug excretion such as liver
and kidney, similar transport pathways have been found in other tissue
s including the intestinal mucosa and the endothelial cells comprising
the blood-brain barrier. Current evidence suggests that these systems
may act as barriers to drug absorption into the tissues in which they
are found. More recent studies have shown that hydrophobic peptides s
uch as cyclosporin A are substrates for polarized efflux. In this revi
ew we examine the evidence for these mechanisms as absorption barriers
and the use of in vitro transport models for characterizing this phen
omenon. The presence of such pathways may help explain the poor membra
ne permeability of peptides which, along with metabolism. contributes
to their poor in vivo performance.