Mechanism of Interaction

- The simultaneous intake of food and drugs can have a strong impact on drug release
and ADME or the, absorption, distribution, metabolism and/or elimination and consequently,
on the efficacy and safety of pharmacotherapy.

Pharmacokinetic Mechanisms
- The most prominent example of a specific pharmacokinetic food-drug effect is the
interaction between grapefruit juice and drugs like cyclosporine and felodipine. 
Cyclosporine metabolite serum concentrations may be significantly increased when
this drug is co-administered with grapefruit juice. In one study exposure to grapefruit
juice increased the mean AUC by 50% for cyclosporine and 236% for
cyclosporin metabolites. You should avoid or limit the consumption of grapefruit
and grapefruit juice if you are receiving treatment with felodipine. Grapefruit juice
can significantly increase the blood levels and effects of medications like felodipine.
You may be more likely to experience side effects such as headache, low blood
pressure, irregular heartbeat, swelling, and fluid retention. 

- The interaction can result through different mechanisms, including the inhibition of
CYP3A4 metabolism as well as inhibition of uptake and efflux membrane transporters. 

Physiologic and Physicochemical Mechanisms

- Dietary substances can alter drug absorption, distribution, metabolism, and/or
excretion (ADME) via physiologic and physicochemical mechanisms.
- Physicochemical mechanisms include binding of the drug by the food.

Biochemical Mechanisms
- Biochemical mechanisms include interference with co-factor formation or function,
potentiation of drug PD, and modification of drug metabolizing enzyme/transporter function
by the dietary substance.

For example, vitamin K-rich foods interfere with cofactor function and should be consumed
cautiously with the anticoagulant, warfarin, as they can disrupt vitamin K metabolism and
increase risk of bleeding or clot formation.
Common causes of Drug-Food Interaction
 Food-induced changes in the bioavailability of the drug
 Bioavailability is an important pharmacokinetic parameter which is correlated with the
clinical effect of most drugs. 
 Food-drug interactions can result in two main clinical effects: either a decreased
bioavailability of a drug, which predisposes to treatment failure, or an increased
bioavailability, which increases the risk of adverse events and may even precipitate
toxicities.
 However, in order to evaluate the clinical relevance of a food-drug interaction the impact
of food intake on the clinical effect of the drug has to be quantified as well.