THE INTERACTIONS BETWEEN GRAPEFRUIT JUICE AND DRUGS

There are many reports about the interactions between grapefruit juice (GJ) and drugs. The finding that GJ can markedly increase oral drug bioavailability was based on an unexpected observation from an interaction study between the felodipine and ethanol, in which GJ was used to mask the taste of ethanol. Subsequent investigations showed that GJ acted by reducing presystemic felodipine metabolism through selective inhibition cytochrome P4503A4 expression in the intestinal wall. The duration of effect of GJ can last 24 h, repeated GJ consumption can result in a cumulative increase in felodipine AUC and Cmax. The high variability of the magnitude of effect among individuals appeared dependent upon inherent differences in enteric CYP3A4 protein expression such that individuals with highest baseline CYP3A4 had the highest proportional increase. At least 20 other drugs have been assessed for an interaction with GJ. Medications with low oral bioavailability because of substantial presystemic metabolism mediated by CYP3A4 appear affected by GJ. Clinically relevant interactions seem likely for most dihydropyridines, terfenadine, saquinavir, cyclosporin, midazolam, triazolam and verapamil and may also occur with lovastatin, cisapride and astemizole. The importance of the interaction appears to be influenced by individual patient susceptibility, type and amount of GJ and administration-related factors. Although in vitro findings support the flavonoid, naringin, or the furanocoumarin, 6',7'-dihydroxybergamottin, as being active ingredients, a final decision on their importance to the interaction must await results from in vivo testing in humans.