Mechanisms of Drug Interactions II: Transport Proteins

  • Darren Michael Moss
  • Marco Siccardi
  • Catia Marzolini
Chapter
Part of the Infectious Disease book series (ID)

Abstract

Most pharmacokinetic studies so far have focused on the role of drug-metabolizing enzymes as the key determinants of drug disposition and their contribution to drug-drug interactions. It has now become clear that transporters are responsible for both the uptake and efflux of drugs in various tissues. Their coordinated expression and activities at the basolateral and apical side of transporting epithelia are critical in determining the extent and direction of drug movement in major organs for drug disposition such as the intestine, liver and kidney. Thus, drug transporters represent an important mechanism by which one drug may alter the pharmacokinetic and pharmacological effects (toxicity and efficacy) of another and lead to drug-drug interactions of clinical importance. This chapter focuses on the major drug transporters mediating the pharmacokinetics of anti-infective agents with special emphasis on their effect on drug disposition, their drug substrate specificities as well as their role in clinically relevant drug-drug interactions.

Keywords

Drug-drug interactions Mechanisms Uptake drug transporters Efflux drug transporters Intestinal absorption Hepatobiliary elimination Renal excretion Tissue distribution Genetic polymorphisms Antiretroviral agents HCV direct-acting antivirals Prediction of drug-drug interactions Physiologically based pharmacokinetic modelling 

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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Darren Michael Moss
    • 1
    • 2
  • Marco Siccardi
    • 1
  • Catia Marzolini
    • 3
  1. 1.Department of Molecular and Clinical PharmacologyUniversity of LiverpoolLiverpoolUK
  2. 2.School of PharmacyKeele UniversityKeeleUK
  3. 3.Division of Infectious Diseases and Hospital EpidemiologyUniversity Hospital Basel and University of BaselBaselSwitzerland

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