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Due to the potential for drug distribution within the liver itself, it is highly unlikely that the volume of distribution of drug in the whole liver at steady state ( V ss,H ) is equal to the volume of distribution of drug in the hepatocyte water ( V hep ) in contact with the drug metabolizing enzymes (Figure 6AβB), and we suggest that the difference of these two volumes of distribution result in the 60β80% of drugs where present IVIVE methods underpredict the in vivo measured clearance
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