INTRODUCTION TO THE SITE

Understanding hepatocyte concentrations of compounds is a new translational topic. In the past, great achievements in the understanding of compound distribution in the liver have been primarily made through the measurement of plasma (as well as urine and faeces) concentrations. Concentrations in target organs were not available. Therefore, when conducting pharmacokinetic studies, the classical approach assumed that unbound concentrations in the liver approximate unbound plasma concentrations. With the emerging knowledge of hepatocyte membrane transporters, it is clear that this assumption is no longer valid. Thus, depending on the relative hepatocyte influx and efflux clearances of compounds, unbound hepatocyte concentrations can exceed, equal, or be lower than unbound plasma concentrations. Disconnection between hepatocyte and plasma concentrations of various endogenous or exogenous compounds becomes even more unpredictable when the expression and functions of membrane transporters are altered during liver diseases.

Hepatocyte concentrations (generated by the transport across influx and efflux membrane proteins) are important for various topics such as drug-drug interactions, drug-induced liver injury, hyperbilirubinemia, cholestatic disorders, inter-individual variability of pharmacokinetics with consequences on drug efficiency and toxicity, multidrug-resistant phenotype of cancers, drug metabolite clearance, and interpretation of liver imaging (PET, SPECT, MRI).

With advances in imaging such as PET, SPECT, and MRI, quantification of human liver concentrations is now possible following the injection of hepatobiliary compounds. Using pharmacokinetic modeling, liver imaging can also predict the function of influx and efflux transporters of hepatocytes.

AIMS OF THE NETWORK

  • To better understand hepatocyte concentrations of compounds cleared by normal and pathologic livers
  • To gather clinicians and researchers from various disciplines with expertise or interest on the topic
  • To increase the visibility of hepatocyte transporter-related research
  • To disseminate the information

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 Please participate as a member or a research group, have your publications uploaded and communicate information to develop the website. Contact: catherine.pastor(at)unige.ch

Catherine web page

Last update: October 2019