Surprisingly, grapefruit juice had the opposite effect: it decreased uptake of fexofenadine by 50% to 90%. 11 Fexofenadine is not metabolized by cytochrome P450 enzymes, but the investigators expected that P-gp inhibition might increase its bioavailability. 10 In 2002, Bailey and colleagues (the same researchers who made the initial discovery of grapefruit juice-drug interactions) designed an investigation to assess the effects of grapefruit, orange, and apple juices on the absorption of the antihistamine fexofenadine (Allegra). Organic anion-transporter polypeptides (OATPs) constitute a family of transport proteins that enhance intestinal absorption of drugs by shuttling them through enterocytes and into circulation. This review summarizes the mechanisms, common medications affected, and practical implications of grapefruit juice-drug interactions to date. 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. 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. 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. 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. 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. 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). The discovery that grapefruit juice could affect the bioavailability of oral medications came quite by accident.
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