Drug-Drug and Food-Drug Interactions of Pharmacokinetic Nature

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 to in the literature or coming from their own clinical experience. The aim of studying DD and FD interactions is to prevent or manage adverse events that can occur during drug treatment. Pharmacological activity depends on adequate drug levels at the action site; however, access to these sites for pharmacokinetic sampling is often limited. Thus, we often rely on plasma concentrations as surrogates to understand exposure–response relationships. Nonetheless, pharmacokinetic interactions may be hidden or imperceptible: sometimes, the drug concentration in plasma remains unaltered, but it could have changed at the action site. The new paradigm should now be that the concentration of either the drug, its metabolites, or any endogenous molecule at the action site could be responsible for the clinical effect. Pharmacokinetics interactions should be dealt with from a wider perspective, not just focusing on research on the administered substance, but on the entire environment conditioning the action.