Drug interactions of grapefruit juice
Grapefruit juice, inhibiting the isoenzyme of the intestinal wall of CYP3A4, has a pronounced effect on the metabolism of a number of drugs, which must be taken into account when prescribing drugs whose concentration in the blood plasma requires careful monitoring.
As data from the last decade of research shows, grapefruit juice can significantly affect the pharmacokinetics of a number of drugs.
A similar effect is associated with the ability of grapefruit to inhibit the activity of the cytochrome P450 isoenzyme CYP3A4, which is included in the metabolism of almost half of all prescribed drugs. Exposure has been shown to be primarily an isoenzyme of the gut wall, although repeated intake (3 times daily) of large amounts of juice (200-240 ml) for several days may also result in inhibition of hepatic isoenzyme. The ability of grapefruit juice to inhibit CYP3A4 is due to the furanocoumarins it contains, bergamottin and 6'7'-dihydroxybergamottine, other components are also possible. Grapefruit juice, apparently, has no pronounced effect on P-glycoprotein, which is involved in the excretion of drugs from the body, but inhibits the polypeptide carrying organic anions, which promotes the absorption of a number of drugs.
Since the inhibitory effect of grapefruit juice is partially irreversible, after a complete evacuation of the juice from the intestine, the enzymatic activity does not recover immediately. Although recovery of half of CYP3A4 activity after taking 1 cup of grapefruit juice is achieved after one day, a weak inhibitory effect persists for an additional 3 days. Thus, the interaction of the juice with drugs cannot be avoided by taking at different times.
The severity of the interaction with the drugs depends to a large extent on the amount of juice consumed. Thus, the daily consumption of 1 cup for 3 days resulted in a doubling of the plasma concentration of lovastatin, and the daily consumption of 3 glasses of concentrated juice for 3 days resulted in a 15-fold increase in the plasma concentration of lovastatin and simvastatin..
The ability to inhibit CYP3A4 may vary depending on the color of the grapefruit (white or pink), when and where it was picked and the consumption of whole fruit, fresh or frozen juice . Although most studies have examined the effects of grapefruit on drug metabolism using frozen juice, fresh grapefruit and several other citrus fruits also contain inhibitors of CYP3A4.
Seville oranges (acids), like grapefruit, contain bergamottin and 6'7'-dihydroxybergamottine, and can interact with drugs metabolized by CYP3A4. Grapefruit, a variety of grapefruit native to India and other Asian countries, has a similar effect. Oranges, tangerines and lemons and the juices they contain have no pronounced inhibitory effect on CYP3A4.
The table shows the main drugs whose metabolism is affected by the use of grapefruit juice, as well as the nature of the effect.
Patients taking drugs whose plasma concentrations require careful monitoring, such as amiodarone, carbamazepine, cyclosporine, sirolimus or tacrolimus, should avoid eating grapefruit, sour oranges and the juices derived from them. For most drugs metabolized by CYP3A4, taking 1 cup of juice or half a grapefruit per day should be considered safe.