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Undesirable Effects of Citrus Juice on the Pharmacokinetics of Drugs

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Abstract

It is well known that intake of grapefruit juice affects the pharmacokinetics of various kinds of drugs. It has been reported that other citrus juices also interact with certain drugs. To re-evaluate citrus juice-drug interactions based on currently available evidence, a literature search was conducted for new and updated information since the grapefruit juice-drug interaction was last reviewed in 1998. MEDLINE (1998–October 2004) was accessed and more than 200 reports were found. The effects of grapefruit juice ingestion on the pharmacokinetics of orally administered drugs have been reported for 40 drugs since the reviews published in 1998. Increases in either area under the concentration-time curve (AUC) or maximum plasma concentration (Cmax) were found with 34 of these, the major mechanism being considered to be inactivation of intestinal cytochrome P450 3A4, a so-called mechanism-based inhibition. Although recent reports point to the inhibitory effects of grapefruit juice on the function of P-glycoprotein, which transports substrates from enterocytes back into the lumen, the contribution to the bioavailability of drugs that are substrates of P-glycoprotein has not been established yet. Dramatic decreases in AUC and Cmax for two drugs in association with grapefruit juice ingestion has been reported and, in these cases, inhibitory effects on organic anion transporting polypeptide, which mediates absorption from the intestinal lumen to enterocytes, might be involved. Other citrus juices such as Seville (sour) orange juice and commonly ingested varieties of orange juice also showed significant effects on the AUC and Cmax of some drugs. Although the situation is complex and uncertainties remain, we recommend that patients avoid citrus juice intake while taking medications and that healthcare providers advise against citrus juice intake in this setting until any interactions with subject drugs can be clarified in clinical studies.

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Notes

  1. GF-I-1 (4-[[6-hydroxy-7-[[1-[(1-hydroxy-1-methyl)ethyl]-4-methyl-6-(7-oxo-7{itH}-furo[3,2-g][1]benzopyran-4-yl)-4-hexenyl]oxy]-3,7-dimethyl-2-octenyl]oxy]-7{itH}-furo[3,2-g][1]benzopyran-7-one)

  2. GF-I-4 (4-[[6-hydroxy-7-[[4-methyl-1-(1-methylethenyl)-6-(7-oxo-7{itH}-furo[3,2-g][1]benzopyran-4-yl)-4-hexenyl]-xy]3,7-dimethyl-2-octenyl]xy]7{itH}-furo[3,2-g][1]benzopyran-7-one)

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Acknowledgements

This work was supported by a grant from the Ministry of Health, Labour and Welfare, Japan. The authors have no conflicts of interest directly relevant to the content of this manuscript.

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  1. Division of Medicinal Safety Science, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan

    Mitsuo Saito, Mutsuko Hirata-Koizumi, Mariko Matsumoto, Tsutomu Urano & Ryuichi Hasegawa

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  1. Mitsuo Saito
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  2. Mutsuko Hirata-Koizumi
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  3. Mariko Matsumoto
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Correspondence to Mitsuo Saito.

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Saito, M., Hirata-Koizumi, M., Matsumoto, M. et al. Undesirable Effects of Citrus Juice on the Pharmacokinetics of Drugs. Drug-Safety 28, 677–694 (2005). https://doi.org/10.2165/00002018-200528080-00003

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