title: Red wine decreases cyclosporine bioavailability.
abstract: 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 Pglycoprotein. 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 (C(max)) 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.
authors.affiliation: School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, MA, USA. stsunoda@u.washington.edu
authors.forename: S M
authors.initials: SM
authors.lastname: Tsunoda
authors.forename: R Z
authors.initials: RZ
authors.lastname: Harris
authors.forename: U
authors.initials: U
authors.lastname: Christians
authors.forename: R L
authors.initials: RL
authors.lastname: Velez
authors.forename: R B
authors.initials: RB
authors.lastname: Freeman
authors.forename: L Z
authors.initials: LZ
authors.lastname: Benet
authors.forename: A
authors.initials: A
authors.lastname: Warshaw
mesh_terms: D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D008297:Male; D006899:Mixed Function Oxygenases / Q000502:physiology; D014920:Wine
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human