This is a very interesting question. There are anecdotal reports of patients being counselled to take their medications with grapefruit juice (GJ) to boost the blood levels of the medication. While this may be appropriate in specific clinical situations, pharmacists should not routinely counsel patients to use GJ to increase the blood levels and effects of their medication.
The most reasonable guideline for pharmacists and other health care professionals to follow is to counsel patients that if they are not currently taking their medications with GJ regularly, don’t start. If they are already taking their medications with GJ regularly, don’t stop. The exceptions to this guideline are for terfenadine (Seldane®), astemizole (Hismanal®) and cisapride (Prepulsid®, Propulsid®), pimozide (Orap®), ziprasidone (Geodon®) and the -statin type cholesterol-lowering drugs known to interact with GJ: lovastatin (Mevacor®), simvastatin (Zocor®), atorvastatin (Lipitor®). Enough evidence exists of the danger of taking terfenadine with GJ that patients should be counselled to avoid these combinations, or to use other medications with similar therapeutic action.
If this interaction is to ever be used therapeutically, it could be with drugs that undergo complete first-pass metabolism, and are therefore only active by the intravenous route. Also, drugs which undergo incomplete first-pass metabolism could be co-administered with GJ to produce more consistent bioavailability and clinical response.4
The exact component of GJ that causes the interaction has been identified as primarily 6'-7-dihydroxybergamottin, though other furanocoumarins such as GF-I-1 and GF-I-4 have been identified.
A company called AvMax is doing research into this area of harnessing GJ components to increase blood levels of medications with low bioavailability. Visit their website at www.avmax.com. Unfortunately, the last post to the AvMax website was in April 2000, and it appears that research by this company has ground to a halt.
A recent study determined that the chemical moiety 5-geranyloxyfurocoumarine is essential for CYP3A4 inhibitory activity. This moiety is found in dihydroxybergamottin, as well as GF-I-1 and GF-I-4. The authors were able to synthesize a stable CYP3A4 inhibitor dihydroxybergamottin caproate, with the same potency as the previously identified GF-I-1 and GF-I-4.127
