Liver Perfusion and Primary Hepatocytes for Studying Drug Metabolism and Metabolite Excretion

This chapter discusses metabolism and excretion within the hepatic systems. It illustrates the localization of hepatobiliary transporters. Hepatic metabolism can have a huge impact on oral bioavailability via the first-pass effect, which can be affected by enzyme and transporter inhibition and induction. This chapter describes liver perfusion and hepatocyte studies and discusses with examples, the utility of each in terms of their ability to elucidate pathways of drug metabolism, drug interactions, and excretion. Organ perfusion is a useful tool for determining the mechanistic aspects of drug clearance and interaction within a particular organ. Liver perfusion provides a closed system, allowing accurate determination of the mass balance of a compound as it relates to disposition by the liver. Primary hepatocytes are a popular and practical in vitro system for drug biotransformation research. Hepatocytes can be isolated from the liver of various animal species by the traditional collagenase perfusion operation developed by Howard and Pesch.