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Effects of Daily Ingestion of Cranberry Juice on the Pharmacokinetics of Warfarin, Tizanidine, and Midazolam—Probes of CYP2C9, CYP1A2, and CYP3A4

2007; Wiley; Volume: 81; Issue: 6 Linguagem: Inglês

10.1038/sj.clpt.6100149

1532-6535

Jari J. Lilja, Janne T. Backman, Pertti J. Neuvonen,

Pharmacology and Obesity Treatment

Case reports suggest that cranberry juice can increase the anticoagulant effect of warfarin. We investigated the effects of cranberry juice on R–S-warfarin, tizanidine, and midazolam; probes of CYP2C9, CYP1A2, and CYP3A4. Ten healthy volunteers took 200 ml cranberry juice or water t.i.d. for 10 days. On day 5, they ingested 10 mg racemic R–S-warfarin, 1 mg tizanidine, and 0.5 mg midazolam, with juice or water, followed by monitoring of drug concentrations and thromboplastin time. Cranberry juice did not increase the peak plasma concentration or area under concentration–time curve (AUC) of the probe drugs or their metabolites, but slightly decreased (7%; P=0.051) the AUC of S-warfarin. Cranberry juice did not change the anticoagulant effect of warfarin. Daily ingestion of cranberry juice does not inhibit the activities of CYP2C9, CYP1A2, or CYP3A4. A pharmacokinetic mechanism for the cranberry juice–warfarin interaction seems unlikely. Clinical Pharmacology & Therapeutics (2007) 81, 833–839. doi:10.1038/sj.clpt.6100149; published online 28 March 2007