Protein Abundance of Clinically Relevant Drug Transporters in the Human Liver and Intestine: A Comparative Analysis in Paired Tissue Specimens

Bioavailability of orally administered drugs is partly determined by function of drug transporters in the liver and intestine. Therefore, we explored adenosine triphosphate–binding cassette (ABC) and solute carriers family transporters expression (quantitative polymerase chain reaction) and protein abundance (liquid chromatography tandem mass spectrometry (LC‐MS/MS)) in human liver and duodenum, jejunum, ileum, and colon in paired tissue specimens from nine organ donors. The transporter proteins were detected in the liver (permeability‐glycoprotein (P‐gp), multidrug resistance protein (MRP)2, MRP3, breast cancer resistance protein (BCRP), organic anion‐transporting polypeptide (OATP)1B1, OATP1B3, OATP2B1, organic cation transporter (OCT)1, OCT3, organic anion transporter 2, Na+‐taurocholate cotransporting polypeptide, monocarboxylate transporter (MCT)1, and multidrug and toxin extrusion 1) and the intestine (P‐gp, multidrug‐resistance protein (MRP)2, MRP3, MRP4, BCRP, OATP2B1, OCT1, apical sodium–bile acid transporter (only ileum), MCT1, and peptide transporter (PEPT1)). Significantly higher hepatic gene expression and protein abundance of ABCC2/MRP2, SLC22A1/OCT1, and SLCO2B1/OATP2B1 were found, as compared to all intestinal segments. No correlations between hepatic and small intestinal protein levels were observed. These observations provide a description of drug transporters distribution without the impact of interindividual variability bias and may help in construction of superior physiologically based pharmacokinetic and humanized animal models.