Inhibition of Hepatic Organic Anion-Transporting Polypeptide by RNA Interference in Sandwich-Cultured Human Hepatocytes: An In Vitro Model to Assess Transporter-Mediated Drug-Drug Interactions

2010 ◽  
Vol 38 (9) ◽  
pp. 1612-1622 ◽  
Author(s):  
Mingxiang Liao ◽  
Arek R. Raczynski ◽  
Michael Chen ◽  
Bei-Ching Chuang ◽  
Qing Zhu ◽  
...  
Keyword(s):  
Rna Interference ◽  
Drug Interactions ◽  
In Vitro Model ◽  
Organic Anion ◽  
Human Hepatocytes ◽  
Organic Anion Transporting Polypeptide ◽  
Vitro Model

scholarly journals Development of a Rat Sandwich-Cultured Hepatocytes Model Expressing Functional Human Organic Anion Transporting Polypeptide (OATP) 1B3: A Potential Screening Tool for Liver-Targeting Compounds

2021 ◽  
Vol 24 ◽  
pp. 475-483
Author(s):  
Taleah Farasyn ◽  
Chao Xu ◽  
Wei Yue
Keyword(s):  
Biliary Excretion ◽  
In Vitro Model ◽  
Organic Anion ◽  
Rat Hepatocytes ◽  
Drug Uptake ◽  
Liver Targeting ◽  
Organic Anion Transporting Polypeptide ◽  
Vitro Model ◽  
In Cells

Purpose: Organic anion transporting polypeptide (OATP) 1B3 transports many clinically important drugs, including statins, from blood into the liver. It exclusively expresses in human liver under normal physiological conditions. There is no rodent ortholog of human OATP1B3. Tissue targeting of therapeutic molecules mediated by transporters, including liver-targeting via liver-specific OATPs, is an emerging area in drug development. Sandwich-cultured primary hepatocytes (SCH) are a well characterized in vitro model for assessment of hepatic drug uptake and biliary excretion. The current study was designed to develop a novel rat SCH model expressing human OATP1B3 to study the hepatic disposition of OATP1B3 substrates. Methods: Primary rat hepatocytes transduced with adenoviral vectors expressing FLAG-tagged OATP1B3 (Ad-OATP1B3), a control vector Ad-LacZ, or that were non-transduced were cultured in a sandwich configuration. FLAG immunoblot and immunofluorescence-staining determined expression and localization of OATP1B3. Uptake of [3H]-cholecystokinin octapeptide (CCK-8), a specific OATP1B3 substrate, was determined. Taurocholate (TC) is a substrate routinely used in SCH to assess biliary excretion via bile canaliculi (BC) and is also a substrate of OATP1B3. [3H]-TC accumulation in cells+BC, cells, biliary excretion index (BEI) and in vitro Clbiliary were determined using B-CLEAR® technology. Results: OATP1B3 protein was extensively expressed and primarily localized on the plasma membrane in day 4 Ad-OATP1B3-transduced rat SCH. [3H]-CCK-8 accumulation in cells+BC was significantly greater (~5-13 folds, p<0.001) in day 4 SCH with vs. without Ad-OATP1B3-transduction. Expressing OATP1B3 in rat SCH significantly increased [3H]-TC accumulation in cells+BC and cells, without affecting BEI and in vitro Clbiliary. Conclusions: Rat SCH expressing human OATP1B3-is a novel in vitro model allowing simultaneous assessment of hepatic uptake, hepatocellular accumulation and biliary excretion process of a human OATP1B3 substrate. This model could be a potential tool for screening for liver-targeting compounds mediated by OATP1B3.

Utility of pooled cryopreserved human enterocytes as an in vitro model for assessing intestinal clearance and drug–drug interactions

2018 ◽  
Vol 33 (1) ◽  
pp. S78 ◽  
Author(s):  
Susan Wong ◽  
Utkarsh Doshi ◽  
Peter Vuong ◽  
Ning Liu ◽  
Suzanne Tay ◽  
...  
Keyword(s):  
Drug Interactions ◽  
In Vitro Model ◽  
Vitro Model

Utility of Pooled Cryopreserved Human Enterocytes as an In vitro Model for Assessing Intestinal Clearance and Drug-Drug Interactions

2018 ◽  
Vol 12 (1) ◽  
pp. 3-13 ◽  
Author(s):  
Susan Wong ◽  
Utkarsh Doshi ◽  
Peter Vuong ◽  
Ning Liu ◽  
Suzanne Tey ◽  
...  
Keyword(s):  
Drug Interactions ◽  
In Vitro Model ◽  
Vitro Model

Utility of Long-Term Cultured Human Hepatocytes as an in Vitro Model for Cytochrome P450 Induction

2006 ◽  
Vol 35 (2) ◽  
pp. 215-220 ◽  
Author(s):  
Georgina Meneses-Lorente ◽  
Christine Pattison ◽  
Claire Guyomard ◽  
Christophe Chesné ◽  
Robert Heavens ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
In Vitro Model ◽  
Human Hepatocytes ◽  
Cytochrome P450 Induction ◽  
Vitro Model

CRYOPRESERVED HUMAN HEPATOCYTES AS ALTERNATIVE IN VITRO MODEL FOR CYTOCHROME P450 INDUCTION STUDIES

2003 ◽  
Vol 39 (7) ◽  
pp. 283 ◽  
Author(s):  
MARTHA GARCIA ◽  
JOSEPH RAGER ◽  
QING WANG ◽  
ROBERT STRAB ◽  
ISMAEL J. HIDALGO ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
In Vitro Model ◽  
Human Hepatocytes ◽  
Cytochrome P450 Induction ◽  
Vitro Model
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