Examination of the role of intestinal fatty acid-binding protein in drug absorption using a parallel artificial membrane permeability assay.
Transcellular diffusion across the absorptive epithelial cells (enterocytes) of the small intestine is the main route of absorption for most orally administered drugs. The process by which lipophilic compounds transverse the aqueous environment of the cytoplasm, however, remains poorly defined. In the present study, we have identified a structurally diverse group of lipophilic drugs that display low micromolar binding affinities for a cytosolic lipid-binding protein - intestinal fatty acid-binding protein (I-FABP). Binding to I-FABP significantly enhanced the transport of lipophilic drug molecules across a model membrane, and the degree of transport enhancement was related to both drug lipophilicity and I-FABP binding affinity. These data suggest that intracellular lipid-binding proteins such as I-FABP may enhance the membrane transport of lipophilic xenobiotics and facilitate drug access to the enterocyte cytoplasm and cytoplasmic organelles.
Velkov
Tony
T
Department of Medicinal Chemistry, Victorian College of Pharmacy, Monash University, Parkville, Victoria 3052, Australia.
Horne
James
J
Laguerre
Aisha
A
Jones
Eric
E
Scanlon
Martin J
MJ
Porter
Christopher J H
CJ
D000818:Animals; D020895:Enterocytes / Q000737:chemistry / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D007408:Intestinal Absorption; D008024:Ligands; D008567:Membranes, Artificial; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D051381:Rats
D050556:Fatty Acid-Binding Proteins; D008024:Ligands; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations