Hidden Sources of Grapefruit in Beverages: Potential Interactions with Immunosuppressant Medications

Abstract

Purpose: The interaction between grapefruit-containing beverages and immunosuppressants is not well defined in the literature. This study was conducted to investigate possible sources of grapefruit juice or grapefruit extract in common US-manufactured beverages. The goal was to identify those products that might serve as hidden sources of dietary grapefruit intake, increasing a transplant patient's risk for drug interactions. Methods: A careful review of the ingredients of the 3 largest US beverage manufacturer's product lines was conducted through manufacturer correspondence, product labeling examination, and online nutrition database research. Focus was placed on citrus-flavored soft drinks, teas, and juice products and their impact on a patient's immunosuppressant regimens. Results: Twenty-three beverages were identified that contained grapefruit. Five did not contain the word ''grapefruit'' in the product name. In addition to the confirmed grapefruit-containing products, 17 products were identified as possibly containing grapefruit juice or grapefruit extract. Conclusion: A greater emphasis should be placed upon properly educating patients regarding hidden sources of grapefruit in popular US beverages and the potential for food-drug interactions. Key Words-drug interaction, grapefruit, immunosuppressionHosp Pharm-2013;48(6):489-493 G rapefruit is an excellent source of vitamins and phytochemicals. Yet, grapefruit has been linked to many significant drug interactions. The well-documented interaction between grapefruit and grapefruit-containing products and certain medications has been attributed to several different potential mechanisms of interaction. The interference of intestinal cytochrome P-450 (CYP 450) enzymes by grapefruit furanocoumarin derivatives is currently accepted as the primary mechanism of interaction. 1The CYP 450 3A4 enzyme is an isoform of the CYP 450 system. The CYP 450 system is a diverse family of over 60 enzymes that function to catalyze the oxidation of organic substances. Cytochromes are the major enzymes through which drug metabolism and bioactivation processes occur, accounting for nearly 75% of these metabolic reactions. Active chemical compounds in grapefruit, known as the furanocoumarins, are primarily responsible for the CYP 450 3A4 interaction. Furanocoumarin derivatives include bermagottin, bergapten, bergaptol, and 6',7'-dihydroxybermagottin.2 Mechanism-based inhibition of CYP 450 3A4 enzymes in the intestine by furanocoumarins results in a complete inactivation of the enzyme. This inhibition of intestinal clearance by CYP3A4 requires de novo restoration of the isoenzyme prior to returning to normal metabolic function.3 With many oral therapeutic agents undergoing first-pass metabolism by CYP 450 3A4, the effects of enzyme inhibition can be significant. Of additional interest is the interference with P-glycoprotein and organic anion transporting peptides by grapefruit bioactive compounds. In contrast to CYP 450 enzyme interference, these mechanisms of interaction are...

A sensitive and specific indirect competitive enzyme-linked immunosorbent assay for the detection of icariin

“…Cross-reactivity (CR) is the most important factor in phytochemical investigations, as there are several structurally-related compounds. In the present study, the assay specificities were examined using icELISA with various associated compounds; the CR% of ICA and the associated compounds were determined according to Weiler's equation (28).…”