Accurately determine the hepatic intrinsic clearance of NCEs taking into account the active uptake into hepatocytes.
The hepatocyte uptake assay is in our portfolio of in vitro ADME services. We deliver consistent, high quality data with the flexibility to adapt protocols based on specific customer requirements.
Experiences of sub-optimal drug exposure due to drug transporter interplay have supported incorporation of studies aimed at understanding the interactions between compound and drug transporters much earlier in drug discovery.
1Riley RJ, Foley SA, Barton P, Soars MG & Williamson B (2016) Expert Opin Drug Metab Toxicol 12(2); 201-216
|Cells||Cryopreserved rat hepatocytes|
|Test Compound Concentration||1 µM (different concentrations available)|
|Incubation Time||0, 0.17, 0.5, 1, 1.5, 2, 5, 10, 20, 30, 60 min|
|Compounds Requirements||50 μL of 10 mM solution|
|Analysis Method||LC-MS/MS quantification|
|Assay Controls||Atorvastatin (positive control for uptake)
Dextromethorphan (negative control for uptake and positive control for CYP activity)
|Data Delivery||Uptake intrinsic clearance (CLint,uptake)
1Riley RJ et al., (2016) Hepatic drug transporters: the journey so far. Expert Opin Drug Metab Toxicol 12(2); 201-216
2Maeda K and Sugiyama Y (2013) Prediction of hepatic transporter-mediated drug-drug interaction from in vitro data. In Transporters in Drug Development – Discovery, Optimization, Clinical Study and Regulation. Ed. Sugiyama Y and Steffansen B. 121-154
3Annaert P et al (2007) Drug Transporters in the Liver. In Drug Transporters: Molecular Characterization and Role in Drug Disposition. Ed. You G and Morris ME. 359-410
4Soars MG et al., (2007) Use of hepatocytes to assess the contribution of hepatic uptake to clearance in vivo. Drug Metab Dispos 35(6); 859-865
5Ishiguro N et al., (2006) Predominant contribution of OATP1B3 to the hepatic uptake of telmisartan, an angiotensin II receptor antagonist, in humans. Drug Metab Dispos 34(7); 1109-1115
6Paine SW et al., (2008) Prediction of the pharmacokinetics of atorvastatin, cerivastatin, and indomethacin using kinetic models applied to isolated rat hepatocytes. Drug Metab Dispos 36(7); 1365-1374
7Gardiner P and Paine SW (2011) The impact of hepatic uptake on the pharmacokinetics of organic anions. Drug Metab Dispos 39(10); 1930-1938
8Ménochet K et al., (2012) Use of mechanistic modelling to assess interindividual variability and interspecies differences in active uptake in human and rat hepatocytes. Drug Metab Dispos 40(9); 1744-1756
9Ménochet K et al., (2012) Simultaneous assessment of uptake and metabolism in rat hepatocytes: a comprehensive mechanistic model. J Pharmacol Exp Ther 341(1); 2-15
10Grime K and Riley RJ (2006) The impact of in vitro binding on in vitro-in vivo extrapolations, projections of metabolic clearance and clinical drug-drug interactions. Curr Drug Metab 7; 251-264
11Hagenbuch B & Meier PJ (2003) The superfamily of organic anion transporting polypeptides. Biochim Biophys Acta 1609(1); 1-18
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