Grapefruit juice-drug interaction and individual variation

Grapefruit juice is a commonly consumed beverage. When administrated simultaneously, grapefruit juice can cause interaction at various degrees with around 40 drugs. The affected drugs vary greatly in therapeutical applications, such as calcium channel blockers, immunosuppressants, HMG CoA reductase inhibitors, HIV protease inhibitors, antihistamines, psychiatric medications, etc. In most cases, the affected drugs are substrates of a subtype of cytochrome P450 3A4(CYP3A4), and show quite low oral bioavailabilities. Thus, it is inferred that the interactions caused by grapefruit juice are due to the inhibition of intestinal CYP3A4. The magnitude of the interaction was highly variable interindividually but reproducible intraindividually. This is believed to be caused by the variation of intestinal CYP3A4 expression among individuals. Recent studies showed that some furanocoumarin derivatives in grapefruit juice are the causing components. And a sour orange juice containing furanocoumarins has shown clear interaction with felodipine similar to that of grapefruit juice. In general, the possible interaction with grapefruit juice should be awared of when using a drug that is lipophilic, selectively metabolized by CYP3A4, administrated at low dosage, and poor of oral bioavailability.