Inhibitory effect of six herbal extracts on CYP2C8 enzyme activity in human liver microsomes

被引：11

作者：

Albassam, Ahmed A. ^{[1
]}

Mohamed, Mohamed-Eslam F. ^{[1
]}

Frye, Reginald F. ^{[1
]}

机构：

[1] Univ Florida, Coll Pharm, Dept Pharmacotherapy & Translat Res, Gainesville, FL 32610 USA

来源：

XENOBIOTICA | 2015年 / 45卷 / 05期

关键词：

Amodiaquine; cranberry; CYP2C8; enzyme inhibition; hydroxypioglitazone; N-desethylamodiaquine; pioglitazone; saw palmetto; CHROMATOGRAPHY MASS-SPECTROMETRY; AUTOMATED ONLINE EXTRACTION; IN-VITRO EVALUATION; CYTOCHROME-P450; ENZYMES; DRUG-INTERACTIONS; LIQUID-CHROMATOGRAPHY; HEALTHY-SUBJECTS; N-DESETHYLAMODIAQUINE; PLASMA-CONCENTRATIONS; CLINICAL-RELEVANCE;

D O I：

10.3109/00498254.2014.989935

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

1. Herbal supplements widely used in the US were screened for the potential to inhibit CYP2C8 activity in human liver microsomes. The herbal extracts screened were garlic, echinacea, saw palmetto, valerian, black cohosh and cranberry. N-desethylamodiaquine (DEAQ) and hydroxypioglitazone metabolite formation were used as indices of CYP2C8 activity. 2. All herbal extracts showed inhibition of CYP2C8 activity for at least one of three concentrations tested. A volume per dose index (VDI) was calculated to determine the volume in which a dose should be diluted to obtain IC50 equivalent concentration. Cranberry and saw palmetto had a VDI value > 5.0 l per dose unit, suggesting a potential for interaction. 3. Inhibition curves were constructed and the IC50 (mean +/- SE) values were 24.7 +/- 2.7 mu g/ml for cranberry and 15.4 +/- 1.7 mu g/ml for saw palmetto. 4. The results suggest a potential for cranberry or saw palmetto extracts to inhibit CYP2C8 activity. Clinical studies are needed to evaluate the significance of this interaction.

引用

页码：406 / 412

页数：7

共 65 条

[1]

Baldwin SJ, 1999, BRIT J CLIN PHARMACO, V48, P424

[2] CYP2C8 and CYP3A4 are the principal enzymes involved in the human in vitro biotransformation of the insulin secretagogue repaglinide [J].

Bidstrup, TB ;

Bjornsdottir, I ;

Sidelmann, UG ;

Thomsen, MS ;

Hansen, KT .

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2003, 56 (03) :305-314

[3] Drug interactions of paclitaxel metabolism in human liver microsomes [J].

Bun, SS ;

Ciccolini, J ;

Bun, H ;

Aubert, C ;

Catalin, J .

JOURNAL OF CHEMOTHERAPY, 2003, 15 (03) :266-274

[4] Effect of gemfibrozil on the pharmacokinetics of pioglitazone [J].

Deng, LJ ;

Wang, F ;

Li, HD .

EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 2005, 61 (11) :831-836

[5] Determination of N-desethylamodiaquine by hydrophilic interaction liquid chromatography with tandem mass spectrometry:: Application to in vitro drug metabolism studies [J].

Dravid, Prajakta V. ;

Frye, Reginald F. .

JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2008, 863 (01) :129-134

[6] The effects of cranberry juice consumption on antioxidant status and biomarkers relating to heart disease and cancer in healthy human volunteers [J].

Duthie, SJ ;

Jenkinson, AM ;

Crozier, A ;

Mullen, W ;

Pirie, L ;

Kyle, J ;

Yap, LS ;

Christen, P ;

Duthie, GG .

EUROPEAN JOURNAL OF NUTRITION, 2006, 45 (02) :113-122

[7] An in vitro evaluation of cytochrome P450 inhibition and P-glycoprotein interaction with goldenseal, Ginkgo biloba, grape seed, milk thistle, and ginseng extracts and their constituents [J].

Etheridge, Amy S. ;

Black, Sherry R. ;

Patel, Purvi R. ;

So, James ;

Mathews, James M. .

PLANTA MEDICA, 2007, 73 (08) :731-741

[8] Moving towards individualized medicine with pharmacogenomics [J].

Evans, WE ;

Relling, MV .

NATURE, 2004, 429 (6990) :464-468

[9]

Food and Drug Administration, 2013, GUID IND BI IN PRESS

[10]

Food and Drug Administration, 2012, GUID IND DR IN PRESS

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