Food–drug interaction: grapefruit juice augments drug bioavailability—mechanism, extent and relevance

Abstract

More than a decade has passed since it was unintentionally discovered that grapefruit juice interacts with certain drugs. The coadministration of these drugs with grapefruit juice can markedly elevate drug bioavailability, and can alter pharmacokinetic and pharmacodynamic parameters of the drug. The predominant mechanism for this interaction is the inhibition of cytochrome P-450 3A4 in the small intestine, resulting in a significant reduction of drug presystemic metabolism. An additional mechanism is, presumably, the inhibition of P-glycoprotein, a transporter that carries drug from the enterocyte back to the gut lumen, resulting in a further increase in the fraction of drug absorbed. Some calcium channel antagonists, benzodiazepines, HMG-CoA reductase inhibitors and cyclosporine are the most affected drugs. A single exposure to one glass of the juice can usually produce the maximal magnitude of the interaction. The data available so far, concerning this interaction and its clinical implications, are reviewed in this article. It is likely that more information regarding this interaction will accumulate in the future, and awareness of such is necessary for achieving optimal drug therapy.

Absorption and pharmacokinetics of grapefruit flavanones in beagles

“…Several studies have shown that grapefruit juice elevates the blood levels of some orally taken drugs, primarily by inhibiting intestinal CYP3A4-mediated first-pass metabolism (Fuhr et al 2002;Dahan & Altman, 2004;Lilja et al 2004;Paine et al 2004Paine et al , 2005, CYP3A4 being a type of cytochrome P450. These studies suggest a potential therapeutic benefit from using the active constituents of grapefruit to increase drug bioavailability.…”

“…These studies suggest a potential therapeutic benefit from using the active constituents of grapefruit to increase drug bioavailability. Lowering the effective dose will also reduce drug costs, although potential clinical problems remain (Dahan & Altman, 2004).…”

Natural Products Modulate the Multifactorial Multidrug Resistance of Cancer

“…One well-documented food-interaction is the altered oral bioavailability of many marketed drugs from co-administered grapefruit juice and citrus fruit [134] [137]. The citrus appear to inhibit the MDR1 and CYP3A4, thus changing the drug absorption in the small intestine [137].…”

Current Perspectives on Sunitinib Targeted Therapy for Tumors

“…Under normal physiological conditions P-gp is widely expressed in many tissues, such as the membrane of endothelial cells in the intestine [38,39], liver [38], placenta [40], blood-brain barrier [41]. Hence, P-gp may play a significant role in drug absorption, disposition, and excretion, as well as in drug-drug and drug-food interactions [42,43]. Additional ATP-binding cassette efflux membrane transporters known to play a role in drug pharmacokinetics are the 190-kDa multidrug resistantassociated protein 2 (MRP2) and the breast cancer resistance protein (BCRP) [44].…”