title: Fatty acid binding proteins: potential chaperones of cytosolic drug transport in the enterocyte?
abstract: OBJECTIVE
  Several poorly water-soluble drugs have previously been shown to bind to intestinal (I-FABP) and liver fatty acid binding protein (L-FABP) in vitro. The purpose of this study was to examine the potential role of drug binding to FABPs on intestinal permeability and gut wall metabolism in vivo.
  
  
  METHODS
  The intestinal permeability of ibuprofen, progesterone and midazolam (which bind FABPs) and propranolol (which does not) was examined using an autoperfused recirculating permeability model in control rats and rats where FABP levels were upregulated via pre-feeding a fat-rich diet.
  
  
  RESULTS
  The intestinal permeability of drugs which bind FABPs in vitro was increased in animals where FABP levels were upregulated by prefeeding a high fat diet. The gut wall metabolism of midazolam was also reduced in animals with elevated FABP levels.
  
  
  CONCLUSIONS
  Consistent with their role in the cellular transport of endogenous lipophilic substrates, FABPs appear to facilitate the intracellular disposition of drug molecules that bind FABPs in vitro. Drug binding to FABPs in the enterocyte may also attenuate gut wall metabolism in a manner analogous to the reduction in hepatic extraction mediated by drug binding to plasma proteins in the systemic circulation.
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Trevaskis
authors.forename: Gary
authors.initials: G
authors.lastname: Nguyen
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Scanlon
authors.forename: Christopher J H
authors.initials: CJ
authors.lastname: Porter
mesh_terms: D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage; D020895:Enterocytes / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D007408:Intestinal Absorption; D007583:Jejunum / Q000166:cytology / Q000378:metabolism*; D008297:Male; D015394:Molecular Structure; D010477:Perfusion; D004364:Pharmaceutical Preparations / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004041:Dietary Fats; D050556:Fatty Acid-Binding Proteins; D004364:Pharmaceutical Preparations