Pomegranate Juice and Pomegranate Extract Do Not Impair Oral Clearance of Flurbiprofen in Human Volunteers: Divergence From In Vitro Results

被引：21

作者：

Hanley, M. J. ^{[1
,2
]}

Masse, G. ^{[1
,2
]}

Harmatz, J. S. ^{[1
,2
]}

Court, M. H. ^{[1
,2
]}

Greenblatt, D. J. ^{[1
,2
]}

机构：

[1] Tufts Univ, Sackler Sch Grad Biomed Sci, Sch Med, Program Pharmacol & Expt Therapeut, Boston, MA 02111 USA

[2] Tufts Med Ctr, Boston, MA USA

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2012年 / 92卷 / 05期

基金：

美国国家卫生研究院;

关键词：

DRUG-DRUG INTERACTIONS; CYTOCHROME-P450 INHIBITION DATA; CRANBERRY JUICE; GRAPEFRUIT JUICE; METABOLISM; WARFARIN; CYP2C9; PHARMACOKINETICS; ANTIOXIDANT; PREDICTION;

D O I：

10.1038/clpt.2012.170

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 (CYP 2C9), with flurbiprofen serving as the index substrate. Fluconazole was the positive control inhibitor. The in vitro 50% inhibitory concentration (IC50) 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 CYP 2C9 in vitro, pomegranate juice and extract had no effect on CYP 2C9 activity in human subjects, and can be consumed by patients taking CYP 2C9 substrate drugs with negligible risk of a pharmacokinetic interaction.

引用

页码：651 / 657

页数：7