Grapefruit juice and drugs interaction

Author: Vito Camarda
Date: 20/02/2013



Grapefruit juice is known to increaese considerably blood drugs concentration after his ingestion., it is believed to interact with them coming even tripling the concentration in the blood, this factor would be to get a triple dose of the drug. A right advice therefore, to avoid the intake of grapefruit juice in these cases, because it is obvious that if the effect of the drug is tripled he may place a whole series of problems, even serious, in overdose.


Grapefruit juice contains flavonoid glycosides (narirutin, naringin., naringinen, quercetin, kaemferol, hesperidin, neohesperidin, didymin, and poncirin) furanocoumarins. and sesquiterpen (nootkatone) all these components can cause irreversible inhibition of the cytochrome P450 enzyme., CYP3A4, mainly in the small intestine.

Cyp 450 is a large multigene family of heme-containing enzymes located in the endoplasmic reticulum of cells throughout the body. It is especially concentrated in the liver and intestinal wall where it is involved in oxidative biotransformation of various endogenous and exogenous substances..
So a lot of drugs are affected by the consumption of grapefruit juice.. The real effect is a reduction in the pre-systemic metabolism of these drugs, which increases their systemic exposure, sometimes by more than 700%. Because inhibition of CYP3A4 is irreversible, it can last for longer than three days after ingestion of grapefruit juice, until new enzyme has been synthesised in the gut wall.

An other mechanism involves the inhibition of a member of the influx transporter protein family (organic anion transporter polypeptide; OATP.). Flavonoids such as naringin and hesperidin have been implicated in the mechanism of OATP inhibition. In contrast to the effect of grapefruit juice on CYP3A4, the inhibition of OATPs shows a clear volume (dose)-response association, which is competitive in nature, with inhibition lasting about four hours. To avoid this interaction just having a four hour gap between the intake of grapefruit juice and drug administration. Drugs affected through this mechanism include aliskiren, celiprolol, fexofenadine, and ciprofloxacin.


Clinical consequences can be very different and an asymptomatic increase in drug concentrations could lead to life threatening events. Such a life threatening event is described in a case report of impaired metabolism of amiodarone after ingestion of grapefruit juice that led to an increase in QT interval and torsades de pointes. Similarly, rhabdomyolysis has been described after coingestion of grapefruit juice with atorvastatin.

These consequences are difficult to predict for individual patients because of it depends on the bioavailability of the drug, the intrinsic level of expression of CYP3A4 or OATPs in the gut, the amount and frequency of grapefruit juice consumption, and the characteristics of the grapefruit juice ingested (fruit species, geographical origin, maturity, manufacturing processes, storage conditions, and seasonal variability). The first of the two mechanisms is most important clinically because of the serious toxic effects that can arise with certain drugs and because the inhibition is irreversible.

For some drugs that are known to interact with grapefruit juice., it has been proposed that the dose given may be reduced; however, it is difficult to predict the consequences of an interaction for different people taking the same drug. Thus, it is probably wise to prescribe an alternative drug that is not affected by grapefruit juice consumption.


Many studies are needed to define which other drugs currently on the market can be affected by grapefruit juice, and to develop better methods to value the severity of the interaction for different people.
Finally, furanocoumarins are also present in Seville oranges and pomelos. Furthermore, other fruits and juices, including cranberry, Goji berry, and apple, contain other active moieties that can affect different P450 isoforms and transporters and interact with different drugs. It is therefore important to take a careful dietary history from patients and provide them with the relevant information to minimise the effects of these potentially serious interactions.

The purpose of many scientists is to exploit this feature of grapefruit juice to obtain the same results assuming a third, or even less, of the drug. In this way not only benefits from an increased effect of the drug but reduces consequently the side effects, given that it assumes in the lower dose.

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