Effect of grapefruit juice on cyclosporine pharmacokinetics

Majeed, Abu Bakar Abdul; Kareem, Ahmed; Bennett, William M.

doi:10.1007/bf00866794

Cited by 5 publications

(2 citation statements)

References 11 publications

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“…The contents of these three grapefruit constituents in commercial juice and fresh grapefruit varied from brand to brand and also from lot to lot. Difference in the concentration of these three constituents, which have potential for drug interaction, which may contribute to the variability in pharmacokinetics of CYP3A4 drugs and some contradictory results of drug interaction studies with grapefruit juice [10].…”

Section: Discussionmentioning

confidence: 99%

Management of Idiopathic Nephrotic Syndrome: Co-Administration of Cyclosporine and Lyophilized Grapefruit Juice

Badria

Elimam

Ibrahim

et al. 2018

NTNF

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Cyclosporine A (CsA) is effective in inducing or maintaining remission in patients with frequently relapsing or steroid-dependent nephrotic syndrome but unfortunately this remission is not long-lasting and most patients relapse within the few months following cessation of treatment. Use of drugs that slow CsA metabolism as ketoconazole was found to be successful in maintaining stable renal function. Certain limitations to the use of ketoconazole such as chronic liver disease, pregnancy and hypersensitivity have favored the potential use of a natural alternative. Grapefruit juice is an inhibitor of the intestinal cytochrome P-450 system, which is responsible for the first-phase metabolism of CsA. Standardized doses of grapefruit as lyophilized capsules (500mg/capsule) were administered concomitantly with CsA to study the changes in CsA pharmacokinetics. The percent rise of CsA exposure as measured by AUC was in the range of 10-25% and co-administration was found to be safe. To find which component is responsible for the observed in vivo interaction, five grapefruit juice components: Quercetin, Naringin, Naringenin, 6, 7-Dihydroxybergamottin (DHB) and Bergamottin (BEG) were screened as potential inhibitors of the metabolism of Saquinavir by human liver microsomes. Both DHB and BEG were found to be potent in vitro inhibitors of the CYP3A4-mediated metabolism of Saquinavir.

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Section: Discussionmentioning

confidence: 99%

Management of Idiopathic Nephrotic Syndrome: Co-Administration of Cyclosporine and Lyophilized Grapefruit Juice

Badria

Elimam

Ibrahim

et al. 2018

NTNF

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“…The most commonly documented immunosuppressant interactions are with grapefruit and cyclosporine [5][6][7][8][9][10][11][12][13] followed by tacrolimus and grapefruit. [14][15][16] Interactions have occurred in patients consuming products that were not known to contain grapefruit.…”

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confidence: 99%

Hidden Sources of Grapefruit in Beverages: Potential Interactions with Immunosuppressant Medications

et al. 2013

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Purpose: The interaction between grapefruit-containing beverages and immunosuppressants is not well defined in the literature. This study was conducted to investigate possible sources of grapefruit juice or grapefruit extract in common US-manufactured beverages. The goal was to identify those products that might serve as hidden sources of dietary grapefruit intake, increasing a transplant patient's risk for drug interactions. Methods: A careful review of the ingredients of the 3 largest US beverage manufacturer's product lines was conducted through manufacturer correspondence, product labeling examination, and online nutrition database research. Focus was placed on citrus-flavored soft drinks, teas, and juice products and their impact on a patient's immunosuppressant regimens. Results: Twenty-three beverages were identified that contained grapefruit. Five did not contain the word ''grapefruit'' in the product name. In addition to the confirmed grapefruit-containing products, 17 products were identified as possibly containing grapefruit juice or grapefruit extract. Conclusion: A greater emphasis should be placed upon properly educating patients regarding hidden sources of grapefruit in popular US beverages and the potential for food-drug interactions. Key Words-drug interaction, grapefruit, immunosuppressionHosp Pharm-2013;48(6):489-493 G rapefruit is an excellent source of vitamins and phytochemicals. Yet, grapefruit has been linked to many significant drug interactions. The well-documented interaction between grapefruit and grapefruit-containing products and certain medications has been attributed to several different potential mechanisms of interaction. The interference of intestinal cytochrome P-450 (CYP 450) enzymes by grapefruit furanocoumarin derivatives is currently accepted as the primary mechanism of interaction. 1The CYP 450 3A4 enzyme is an isoform of the CYP 450 system. The CYP 450 system is a diverse family of over 60 enzymes that function to catalyze the oxidation of organic substances. Cytochromes are the major enzymes through which drug metabolism and bioactivation processes occur, accounting for nearly 75% of these metabolic reactions. Active chemical compounds in grapefruit, known as the furanocoumarins, are primarily responsible for the CYP 450 3A4 interaction. Furanocoumarin derivatives include bermagottin, bergapten, bergaptol, and 6',7'-dihydroxybermagottin.2 Mechanism-based inhibition of CYP 450 3A4 enzymes in the intestine by furanocoumarins results in a complete inactivation of the enzyme. This inhibition of intestinal clearance by CYP3A4 requires de novo restoration of the isoenzyme prior to returning to normal metabolic function.3 With many oral therapeutic agents undergoing first-pass metabolism by CYP 450 3A4, the effects of enzyme inhibition can be significant. Of additional interest is the interference with P-glycoprotein and organic anion transporting peptides by grapefruit bioactive compounds. In contrast to CYP 450 enzyme interference, these mechanisms of interaction are...

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Grapefruit: the last decade acquisitions

Tirillini

2000

Fitoterapia

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Effect of grapefruit juice on cyclosporine pharmacokinetics

Cited by 5 publications

References 11 publications

Management of Idiopathic Nephrotic Syndrome: Co-Administration of Cyclosporine and Lyophilized Grapefruit Juice

Management of Idiopathic Nephrotic Syndrome: Co-Administration of Cyclosporine and Lyophilized Grapefruit Juice

Hidden Sources of Grapefruit in Beverages: Potential Interactions with Immunosuppressant Medications

Grapefruit: the last decade acquisitions

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