Cytochrome P450 3A4 is particularly essential, because it is involved in the bioinactivation of about 50% of all drugs.

The most important is drug metabolism involving oxidation by enzymes belonging to the cytochrome P450 superfamily. The actions of drugs are terminated through several biological mechanisms. What are the key scientific concepts of grapefruit–drug interactions? The measured outcome from these studies was change in drug pharmacokinetics, and this was used to assess the potential for adverse clinical consequences. Most of the information was from randomized controlled clinical trials ( n = 102). We assessed the following sections of these documents for relevant information: “Summary Product Information,” “Warnings and Precautions,” “Contraindications,” “Adverse Reactions,” “Drug Interactions” and “Action and Clinical Pharmacology.” We identified 190 relevant publications (161 articles from PubMed 29 product monographs or prescribing information sheets). We conducted a comprehensive search of the PubMed database for all available scientifically valid evidence using the keyword “grapefruit” and the following additional terms: “drug,” “drug interaction,” “pharmacokinetics,” “cytochrome P450,” “CYP3A4,” “case report” or “review.” In addition, we obtained product monographs and prescribing information for drugs recently introduced (i.e., in the last 4 yr) to the Canadian market. A summary of the evidence used in this review, which comes mainly from randomized controlled trials, is found in Box 1. 4 However, we will focus on the most well-known and well-studied interaction: that of interference in the activity of the cytochrome P450 3A4 (CYP3A4) enzyme. It was recently found that grapefruit and certain other citrus juices act by an additional mechanism to cause diminished systemic concentration of certain drugs by inhibiting drug transporters. We focus on grapefruit because it is the most widely examined, but other citrus fruits may have similar consequences. This review identifies the key scientific concepts and clinical implications of grapefruit–drug interactions relevant to medical practice.

This increase is a result of the introduction of new chemical entities and formulations. Between 20, the number of medications with the potential to interact with grapefruit and cause serious adverse effects (i.e., torsade de pointes, rhabdomyolysis, myelotoxicity, respiratory depression, gastrointestinal bleeding, nephrotoxicity) has increased from 17 to 43, representing an average rate of increase exceeding 6 drugs per year. Recently, however, a disturbing trend has been seen. Many of the drugs that interact with grapefruit are highly prescribed and are essential for the treatment of important or common medical conditions. This interaction enhances systemic drug concentration through impaired drug metabolism.

1 – 3 Currently, more than 85 drugs, most of which are available in Canada, are known or predicted to interact with grapefruit. Our research group discovered the interaction between grapefruit and certain medications more than 20 years ago.

Grapefruit juice interactions