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Grapefruit-Drug Interactions

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Abstract

Grapefruit juice and grapefruit product consumption have potential health benefits; however, their intake is also associated with interactions with certain drugs, including calcium channel blockers, immunosuppressants and antihistamines. The primary mechanism through which interactions are mediated is mechanism-based intestinal cytochrome P450 3A4 inhibition by furanocoumarins resulting in increased bioavailability of administered medications that are substrates. Grapefruit products have also been associated with interactions with P-glycoprotein (P-gp) and uptake transporters (e.g. organic anion-transporting polypeptides [OATPs]). Polyphenolic compounds such as flavonoids have been proposed as the causative agents of the P-gp and OATP interactions. The mechanisms and magnitudes of the interactions can be influenced by the concentrations of furanocoumarins and flavonoids in the grapefruit product, the volume of juice consumed, and the inherent variability of specific enzymes and transporter components in humans. It is therefore challenging to predict the extent of grapefruit product-drug interactions and to compare available in vitro and in vivo data. The clinical significance of such interactions also depends on the disposition and toxicity profile of the drug being administered. The aim of this review is to outline the mechanisms of grapefruit-drug interactions and present a comprehensive summary of those agents affected and whether they are likely to be of clinical relevance.

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Acknowledgments

The authors thank the National Institute of Health Research (NIHR-Department of Health) and the Northwest Development Agency (NWDA) for infrastructural and project support.

Transparency declaration: This review was in part funded by the Florida Department of Citrus (FDOC).

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Authors and Affiliations

  1. NIHR Biomedical Research Centre, Royal Liverpool and Broadgreen University Hospital Trust, Liverpool, UK

    Kay Seden & Laura Dickinson

  2. Department of Pharmacology, University of Liverpool, Block H, First Floor 70 Pembroke Place, Liverpool, L69 3GF, UK

    Kay Seden, Laura Dickinson, Saye Khoo & David Back

  3. Pharmacy Department, Royal Liverpool University Hospital, Liverpool, UK

    Kay Seden

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  1. Kay Seden
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  2. Laura Dickinson
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Correspondence to Kay Seden.

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Seden, K., Dickinson, L., Khoo, S. et al. Grapefruit-Drug Interactions. Drugs 70, 2373–2407 (2010). https://doi.org/10.2165/11585250-000000000-00000

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