title: Meta-analysis of expression of hepatic organic anion-transporting polypeptide (OATP) transporters in cellular systems relative to human liver tissue.
abstract: Organic anion-transporting polypeptide (OATP)1B1, OATP1B3, and OATP2B1 transporters play an important role in hepatic drug disposition. Recently, an increasing number of studies have reported proteomic expression data for OATP transporters. However, systematic analysis and understanding of the actual differences in OATP expression between liver tissue and commonly used cellular systems is lacking. In the current study, meta-analysis was performed to assess the protein expression of OATP transporters reported in hepatocytes relative to liver tissue and to identify any potential correlations in transporter expression levels in the same individual. OATP1B1 was identified as the most abundant uptake transporter at 5.9 ± 8.3, 5.8 ± 3.3, and 4.2 ± 1.7 fmol/μg protein in liver tissue, sandwich-cultured human hepatocytes (SCHH), and cryopreserved suspended hepatocytes, respectively. The rank order in average expression in liver tissue and cellular systems was OATP1B1 > OATP1B3 ≈ OATP2B1. Abundance levels of the OATP transporters investigated were not significantly different between liver and cellular systems, with the exception of OATP2B1 expression in SCHH relative to liver tissue. Analysis of OATP1B1, OATP1B3, and OATP2B1 liver expression data in the same individuals (n = 86) identified weak (OATP1B1-OATP2B1) to moderately (OATP1B3-OATP2B1) significant correlations. A significant weak correlation was noted between OATP1B1 abundance and age of human donors, whereas expression of the OATPs investigated was independent of sex. Implications of the current analysis on the in vitro-in vivo extrapolation of transporter-mediated drug disposition using physiologically based pharmacokinetic models are discussed.
authors.affiliation: Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, The University of Manchester, Manchester, United Kingdom (J.B., B.A., A.R-H., A.G.) and Simcyp Limited (a Certara Company), Sheffield, United Kingdom (A.R-H.).
authors.forename: Justine
authors.initials: J
authors.lastname: Badée
authors.affiliation: Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, The University of Manchester, Manchester, United Kingdom (J.B., B.A., A.R-H., A.G.) and Simcyp Limited (a Certara Company), Sheffield, United Kingdom (A.R-H.).
authors.forename: Brahim
authors.initials: B
authors.lastname: Achour
authors.affiliation: Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, The University of Manchester, Manchester, United Kingdom (J.B., B.A., A.R-H., A.G.) and Simcyp Limited (a Certara Company), Sheffield, United Kingdom (A.R-H.).
authors.forename: Amin
authors.initials: A
authors.lastname: Rostami-Hodjegan
authors.affiliation: Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, The University of Manchester, Manchester, United Kingdom (J.B., B.A., A.R-H., A.G.) and Simcyp Limited (a Certara Company), Sheffield, United Kingdom (A.R-H.) Aleksandra.Galetin@manchester.ac.uk.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Galetin
mesh_terms: D000375:Aging / Q000378:metabolism; D018929:Cell Culture Techniques; D003627:Data Interpretation, Statistical; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters / Q000096:biosynthesis*; D029362:Organic Anion Transporters, Sodium-Independent / Q000096:biosynthesis*; D004364:Pharmaceutical Preparations / Q000378:metabolism; D040901:Proteomics / Q000379:methods* / Q000706:statistics & numerical data; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D014018:Tissue Distribution
chemical_list: D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent; D004364:Pharmaceutical Preparations; C503999:SLCO1B1 protein, human; C421209:SLCO1B3 protein, human; C450859:SLCO2B1 protein, human; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3