Grapefruit juice and drug interactions. Exploring mechanisms of this interaction and potential toxicity for certain...

Concomitant administration of grapefruit juice can increase the plasma concentration of numerous drugs in humans and decrease the concentration of a few others. Such elevations of drug plasma concentrations have, on occasion, resulted in adverse clinical effects. Increased concentrations are primarily mediated by chemicals in grapefruit juice, which inhibit the CYP 3A4 drug-metabolizing enzyme in the small intestines. This inhibition decreases the first-pass metabolism of drugs using the CYP 3A4 intestinal system and increases the bioavailability and maximal plasma drug concentrations (Cmax) of the CYP 3A4 substrates. The effect of grapefruit juice on drug metabolism is most pronounced in drugs with a high first-pass metabolism (eg, felodipine, amiodarone), in which it inhibits the first-pass metabolism of the CYP 3A4 substrates leading to an increase in Cmax and area under the concentration time curve (AUC). The use of grapefruit juice with a few specific drugs (eg, fexofenadine, digoxin) may lower plasma drug concentrations by inhibiting drug absorption catalyzed by the organic anion transporting polypeptide (OATP).