Red wine decreases cyclosporine bioavailability

Background Many commonly ingested substances such as grapefruit juice and Hypericum perforatum (St John's wort) have been found to interact with important therapeutic agents such as cyclosporine (INN, ciclosporin). The mechanism for these interactions is thought to involve modulation of the act...

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Veröffentlicht in:Clinical pharmacology and therapeutics 2001-11, Vol.70 (5), p.462-467
Hauptverfasser: Tsunoda, Shirley M., Harris, Robert Z., Christians, Uwe, Velez, Rebecca L., Freeman, Richard B., Benet, Leslie Z., Warshaw, Abigail
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Sprache:eng
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Zusammenfassung:Background Many commonly ingested substances such as grapefruit juice and Hypericum perforatum (St John's wort) have been found to interact with important therapeutic agents such as cyclosporine (INN, ciclosporin). The mechanism for these interactions is thought to involve modulation of the activity of the drug‐metabolizing enzyme cytochrome P4503A4 (CYP3A4) and/or the drug transport protein P‐glycoprotein. In vitro data suggest that red wine may interact with CYP3A4 substrates such as cyclosporine. Methods We conducted a randomized, 2‐way crossover study of 12 healthy individuals. Subjects received a single 8‐mg/kg dose of oral cyclosporine with water (control) and with 12 oz of red wine (Blackstone Merlot 1996; Blackstone Winery, Graton, Calif). Whole blood was analyzed for cyclosporine and 6 metabolites by specific fluorescence polarization immunoassay and tandem liquid chromatography‐mass spectrometry. Blood levels of cyclosporine were compared between the 2 arms. Results Red wine caused a 50% increase in the oral clearance of cyclosporine. Systemic exposure as measured by the area under the concentration‐versus‐time curve (AUC) and peak concentration (Cmax) were significantly decreased by red wine. However, half‐life was not affected, suggesting that red wine decreased cyclosporine absorption. In vitro, the solubility of cyclosporine in red wine appeared to be lower than in water. Conclusions Administration of cyclosporine with red wine causes a significant decrease in cyclosporine exposure. Because cyclosporine is a narrow therapeutic range compound, caution may be warranted with concomitant intake of red wine and cyclosporine. Clinical Pharmacology & Therapeutics (2001) 70, 462–467; doi: 10.1016/S0009‐9236(01)70992‐7
ISSN:0009-9236
1532-6535
DOI:10.1016/S0009-9236(01)70992-7