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 impo rtant therapeutic agents such as cyclosporine (INN, ciclosporin). The mecha nism for these interactions is thought to involve modulation of the activit y of the drug-metabolizing enzyme cytochrome P4503A4 (CYP3A4) and/or the dr ug transport protein P-glycoprotein. In vitro data suggest that red wine ma y interact with CYP3A4 substrates such as cyclosporine. Methods: We conducted a randomized, 2-way crossover study of 12 healthy ind ividuals. Subjects received a single 8-mg/kg dose of oral cyclosporine with water (control) and with 12 oz of red wine (Blackstone Merlot, 1996; Black stone 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 cyclospori ne. Systemic exposure as measured by the area under the concentration-versu s-time curve (AUC) and peak concentration (C-max) were significantly decrea sed by red wine. However, half-life was not affected, suggesting that red w ine decreased cyclosporine absorption. In vitro, the solubility of cyclospo rine in red wine appeared to be lower than in water. Conclusions: Administration of cyclosporine with red wine causes a signific ant decrease in cyclosporine exposure. Because cyclosporine is a narrow the rapeutic range compound, caution may be warranted with concomitant intake o f red wine and cyclosporine.