Fatty Acid Binding Proteins: Potential Chaperones of Cytosolic Drug Transport in the Enterocyte?

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2011 Apr 28

PMID 21523511

Citations 8

Authors

Natalie L Trevaskis

Gary Nguyen

Martin J Scanlon

Christopher J H Porter

Affiliations

Soon will be listed here.

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.

Citing Articles

Drugs Form Ternary Complexes with Human Liver Fatty Acid Binding Protein 1 (FABP1) and FABP1 Binding Alters Drug Metabolism.

Yabut K, Martynova A, Nath A, Zercher B, Bush M, Isoherranen N Mol Pharmacol. 2024; 105(6):395-410.

PMID: 38580446 PMC: 11114116. DOI: 10.1124/molpharm.124.000878.

Drugs Form Ternary Complexes with Human Liver Fatty Acid Binding Protein (FABP1) and FABP1 Binding Alters Drug Metabolism.

Yabut K, Martynova A, Nath A, Zercher B, Bush M, Isoherranen N bioRxiv. 2024; .

PMID: 38293009 PMC: 10827205. DOI: 10.1101/2024.01.17.576032.

PBPK Modeling Approach to Predict the Behavior of Drugs Cleared by Metabolism in Pregnant Subjects and Fetuses.

Le Merdy M, Szeto K, Perrier J, Bolger M, Lukacova V Pharmaceutics. 2024; 16(1).

PMID: 38258106 PMC: 10820132. DOI: 10.3390/pharmaceutics16010096.

Impact of Intracellular Lipid Binding Proteins on Endogenous and Xenobiotic Ligand Metabolism and Disposition.

Yabut K, Isoherranen N Drug Metab Dispos. 2023; 51(6):700-717.

PMID: 37012074 PMC: 10197203. DOI: 10.1124/dmd.122.001010.

Lipids and Lipid-Processing Pathways in Drug Delivery and Therapeutics.

Markovic M, Ben-Shabat S, Aponick A, Zimmermann E, Dahan A Int J Mol Sci. 2020; 21(9).

PMID: 32375338 PMC: 7247327. DOI: 10.3390/ijms21093248.

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