Grapefruit: A food that potently impairs intestinal drug metabolism and uptake transport clinically


David G. Bailey, Division of Clinical Pharmacology, Department of Medicine, London Health Sciences Centre and Department of Physiology & Pharmaco, University of Western Ontario, 375 South St, London, ON N6A 4G5
The 1991 report that grapefruit juice caused 3-fold higher oral bioavailability of the antihypertensive medication, felodipine, provided the primary important clinical example of food-mediated inactivation of first-pass drug metabolism. Many scientists subsequently significantly contributed to the understanding of this type of interaction. More than 40 medications, some of which are highly prescribed or essential medications, now appear to carry the risk of a grapefruit - induced adverse drug interaction. Recently, grapefruit juice was also shown to lower the oral bioavailability of other drugs through inhibition of a specific intestinal uptake transporter. For each type of interaction, the discovery, mechanism and active ingredient(s) will be reviewed. Clinically relevant issues (volume-effect relationships, individual variability and reproducibility, duration of effect, repeated juice consumption, age and affected drugs) will be discussed. The action of other fruit juices and the potential clinical usefulness of inclusion of the active ingredient(s) into drug formulations will be considered.