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Author: Admin | 2025-04-28
The practical implications of grapefruit juice's interactions with more than 85 medicationsThe serendipitous discovery that grapefruit juice could dramatically increase the bioavailability of orally administered medications resulted from the findings of a 1989 clinical trial on the pharmacodynamics of felodipine. Grapefruit juice is now estimated to pose a nutrient-drug interaction with more than 85 different medications. The primary mechanism of this interaction is inhibition of cytochrome P450 3A4 (CYP3A4), but grapefruit juice also inhibits organic anion-transporter polypeptides (OATPs). These mechanisms can increase bioavailability, decrease bioavailability, or reduce the metabolic activation of certain medications. Many commonly prescribed drugs interact with grapefruit juice, and these interactions can produce clinically significant effects. Consumption of a single glass of juice is sufficient to alter drug metabolism, and the effect can last as long as 3 days. Practical implications of grapefruit juice-drug interactions are reviewed here. AbstractThe serendipitous discovery that grapefruit juice could dramatically increase the bioavailability of orally administered medications resulted from the findings of a 1989 clinical trial on the pharmacodynamics of felodipine. Grapefruit juice is now estimated to pose a nutrient-drug interaction with more than 85 different medications. The primary mechanism of this interaction is inhibition of cytochrome P450 3A4 (CYP3A4), but grapefruit juice also inhibits organic anion-transporter polypeptides (OATPs). These mechanisms can increase bioavailability, decrease bioavailability, or reduce the metabolic activation of certain medications. Many commonly prescribed drugs interact with grapefruit juice, and these interactions can produce clinically significant effects. Consumption of a single glass of juice is sufficient to alter drug metabolism, and the effect can last as long as 3 days. Practical implications of grapefruit juice-drug interactions are reviewed here.IntroductionThe discovery that grapefruit juice could affect the bioavailability of oral medications came quite by accident. In 1989, David Bailey and his colleagues at the University of Western Ontario designed a study to assess the interaction between ethanol and the calcium channel blocker felodipine (Plendil).1 Following an evening of taste-testing from the home refrigerator, assuming that fruit juice would not affect the outcome, they chose white grapefruit as the most effective vehicle to mask the flavor of ethanol for this study.2 To their surprise, when the medication was taken with nonintoxicating amounts of grapefruit juice-flavored ethanol, Bailey and his colleagues detected felodipine concentrations severalfold higher than previous studies would have predicted. This unexpected finding led to subsequent investigations and a 1991 publication in the Lancet, which reported an almost 3-fold increased bioavailability of felodipine when taken with grapefruit juice.3 Felodipine is the most extensively studied medication related to grapefruit juice-drug interactions, but hundreds of studies and articles have been written on this topic since its initial discovery more than 25 years ago. While grapefruit juice is best known for its ability to increase plasma drug concentrations, more recent research has identified situations where it has the opposite effect. This review summarizes the mechanisms, common medications affected, and practical implications of grapefruit juice-drug interactions to date.MechanismsFelodipine and other related calcium channel blockers undergo considerable first-pass metabolism in the small intestine and
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