Drug interactions with grapefruit juice.
Some drugs demonstrate a significantly greater (up to 3-fold) mean oral bioavailability on coadministration with grapefruit juice. With some calcium antagonists, the benzodiazepines midazolam and triazolam and the antihistamine terfenadine, changes in bioavailability are accompanied by altered drug action. Study design factors possibly contribute to the magnitude of changes in drug bioavailability; they include the source of the citrus, its intake schedule, drug formulations and individual metabolising capacity. The components of citrus juice that are responsible for clinical drug interactions have yet to be fully determined. Based on the flavonoid naringin's unique distribution in the plant kingdom, abundance in grapefruit and ability to inhibit metabolic enzymes, naringin is likely to be one of the grapefruit components influencing drug metabolism. Other components present in citrus fruit, such as furanocoumarins, may be more potent inhibitors than flavonoids and are under investigation. Conclusions drawn from clinical drug interaction studies should be considered specific to the citrus fruit products evaluated because of the variation in their natural product content. The predominant mechanism for enhanced bioavailability is presumably the inhibition of oxidative drug metabolism in the small intestine. The consistent findings across studies of diverse cytochrome P450 (CYP) 3A substrates support the mechanistic hypothesis that 1 or more grapefruit juice components inhibit CYP3A enzymes in the gastrointestinal tract. The evaluation of the need to avoid the concomitant intake of grapefruit products with drugs is best done on an individual drug basis rather than collectively by drug class. Based on the narrow therapeutic range of cyclosporin and research experience in organ transplant recipients, its interaction with grapefruit juice is likely to be clinically significant.
Ameer
B
B
Princeton Junction, New Jersey, USA.
Weintraub
R A
RA
D014151:Anti-Anxiety Agents / Q000378:metabolism; D001628:Beverages; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000378:metabolism; D002957:Citrus / Q000378:metabolism*; D018849:Controlled Clinical Trials as Topic; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005419:Flavonoids / Q000378:metabolism; D018565:Food-Drug Interactions; D041743:Herb-Drug Interactions; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism; D066298:In Vitro Techniques; D008874:Midazolam / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism
D014151:Anti-Anxiety Agents; D002121:Calcium Channel Blockers; D000697:Central Nervous System Stimulants; D004967:Estrogens; D005419:Flavonoids; D007166:Immunosuppressive Agents; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D008874:Midazolam