title: Pomegranate juice and pomegranate extract do not impair oral clearance of flurbiprofen in human volunteers: divergence from in vitro results.
abstract: Nutrient interactions with prescription drugs are a topic of ongoing basic and clinical research. Pomegranate juice and a 1-g capsule containing pomegranate extract were evaluated in vitro and in vivo as inhibitors of cytochrome P450 2C9 (CYP2C9), with flurbiprofen serving as the index substrate. Fluconazole was the positive control inhibitor. The in vitro 50% inhibitory concentration (IC(50)) values for pomegranate juice and extract were below 1% (vol/vol), with no evidence of mechanism-based (irreversible) inhibition. In clinical studies, flurbiprofen pharmacokinetics were unchanged by pomegranate juice or extract as compared to a low-polyphenol placebo control beverage. However, fluconazole significantly reduced the oral clearance of flurbiprofen. Despite inhibition of CYP2C9 in vitro, pomegranate juice and extract had no effect on CYP2C9 activity in human subjects, and can be consumed by patients taking CYP2C9 substrate drugs with negligible risk of a pharmacokinetic interaction.
authors.affiliation: Program in Pharmacology and Experimental Therapeutics, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Hanley
authors.forename: G
authors.initials: G
authors.lastname: Masse
authors.forename: J S
authors.initials: JS
authors.lastname: Harmatz
authors.forename: M H
authors.initials: MH
authors.lastname: Court
authors.forename: D J
authors.initials: DJ
authors.lastname: Greenblatt
mesh_terms: D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D001628:Beverages; D065729:Cytochrome P-450 CYP2C9; D005260:Female; D015725:Fluconazole / Q000494:pharmacology; D005480:Flurbiprofen / Q000493:pharmacokinetics*; D018565:Food-Drug Interactions; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D029561:Lythraceae / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D010936:Plant Extracts / Q000494:pharmacology; D055815:Young Adult
chemical_list: D010936:Plant Extracts; D005480:Flurbiprofen; D015725:Fluconazole; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases