caa a22 4500 445312068 CHVBK 20180317142633.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s11095-011-0446-1 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0446-1 Fatty Acid Binding Proteins: Potential Chaperones of Cytosolic Drug Transport in the Enterocyte? [Elektronische Daten] [Natalie Trevaskis, Gary Nguyen, Martin Scanlon, Christopher Porter] ABSTRACT: Purpose: 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. Springer Science+Business Media, LLC, 2011 drug absorption nationallicence drug metabolism nationallicence fatty acid binding protein nationallicence intestinal permeability nationallicence poorly water-soluble drugs nationallicence FABPs : fatty acid binding proteins nationallicence I-FABP : intestinal FABP nationallicence iLBP : intracellular lipid binding proteins nationallicence L-FABP : liver FABP nationallicence Trevaskis Natalie Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, 3052, Parkville, Victoria, Australia aut Nguyen Gary Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, 3052, Parkville, Victoria, Australia aut Scanlon Martin Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, 3052, Parkville, Victoria, Australia aut Porter Christopher Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, 3052, Parkville, Victoria, Australia aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/9(2011-09-01), 2176-2190 0724-8741 28:9<2176 2011 28 11095 https://doi.org/10.1007/s11095-011-0446-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0446-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Trevaskis Natalie Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, 3052, Parkville, Victoria, Australia aut NATIONALLICENCE 700 1- Nguyen Gary Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, 3052, Parkville, Victoria, Australia aut NATIONALLICENCE 700 1- Scanlon Martin Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, 3052, Parkville, Victoria, Australia aut NATIONALLICENCE 700 1- Porter Christopher Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, 3052, Parkville, Victoria, Australia aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/9(2011-09-01), 2176-2190 0724-8741 28:9<2176 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer