In vitro–in vivo extrapolation of hepatic clearance: Biological tools, scaling factors, model assumptions and correct concentrations

@article{Pelkonen2007InVV,
  title={In vitro–in vivo extrapolation of hepatic clearance: Biological tools, scaling factors, model assumptions and correct concentrations},
  author={Olavi Pelkonen and M Turpeinen},
  journal={Xenobiotica},
  year={2007},
  volume={37},
  pages={1066 - 1089}
}
Although the measurement of metabolite formation or substrate depletion in in vitro systems, from recombinant enzymes to tissue slices, is a relatively routine task, there are a number of more or less unresolved issues in the extrapolation of the enzymatic intrinsic clearance into hepatic metabolic clearance. Nominal concentrations of the drug added to the incubation system are not necessarily the concentration the transporter or the metabolizing enzyme sees. In addition, peculiarities of… 
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