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Review Article Open Access
The significance of the use of grapefruit juice as i t relates to drug-drug interaction potential, via cytochrome P450 (CYP) 3A4 isozyme, has been a topic of considerable interest for over a decade now. Drugs belonging to diversified chemical classes have exhibited a significant pharmacokinetic and/or pharmacodynamic interaction when concomitantly administered with grapefruit juice. Owing to the inhibition of the intestinal CYP 3A4 enzyme, the exposure levels of the ingested drug substrate have been increased by several folds following a single intake of grapefruit juice. While many investigations have been performed to identify active ingredient(s) in grapefruit juice responsible for this profound interaction resulting in an increased bioavailability, some recent reports suggest that grapefruit juice may impede the bioavailability of a very few drugs due to alteration of the micro-environment of absorption. Therefore, from a clinical viewpoint, caution needs to be exercised when co-administering CYP 3A4 substrates with grapefruit juice. Additionally, molecules that are substrates to P-glycoprotein efflux transporter pumps may also get affected by the inhibitory interaction of grapefruit juice. In some situations, the inhibitory interaction exerted by grapefruit juice may be capitalized to allow dose reduction of CYP3A4 substrate(s). This review covers many aspects of drug-drug interaction potential upon the ingestion of grapefruit juice.
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Author(s): N R Srinivas