Drug-Drug and Food-Drug Interactions of Pharmacokinetic Nature

  • Pietro FagiolinoEmail author
  • Marta Vázquez
  • Manuel Ibarra
  • Cecilia Maldonado
  • Rosa Eiraldi


The most relevant pharmacokinetic mechanisms of drug-drug (DD) and food-drug (FD) interactions are summarized from a perspective that will allow the readers to apply the concepts exposed here to other cases referred in the literature or coming from their own clinical experience. The aim of studying DD and FD interactions is to prevent, or to manage, eventual adverse events that can appear during drug treatments. Pharmacological activity depends on adequate drug levels at the action site, but access to these sites for pharmacokinetic sampling is often limited. Thus, we often rely on plasma concentrations as surrogates in efforts to understand exposure-response relationships. However, pharmacokinetic interactions may be hidden or imperceptible. Sometimes, drug concentration in plasma remains unaltered, but it could have changed at the action sites. The new paradigm should now be that the concentration of either the drug, or its metabolite, or any endogenous molecule at the action sites, is always responsible for the clinical effect. Then, pharmacokinetic interaction should be dealt with a wider perspective, not just focusing the research on the administered substance but on the entire environment conditioning the action.


Plasma protein binding Membrane transporter and enzyme Inducers and inhibitors Environmental pH Sex-related gastrointestinal differences Food effect on bioavailability and bioequivalence 


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© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Pietro Fagiolino
    • 1
    Email author
  • Marta Vázquez
    • 1
  • Manuel Ibarra
    • 1
  • Cecilia Maldonado
    • 1
  • Rosa Eiraldi
    • 1
  1. 1.Pharmaceutical Sciences Department, Faculty of ChemistryUniversidad de La RepúblicaMontevideoUruguay

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