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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-38855

Hajda, J; Rentsch, K M; Gubler, C; Steinert, H; Stieger, B; Fattinger, K (2010). Garlic extract induces intestinal P-glycoprotein, but exhibits no effect on intestinal and hepatic CYP3A4 in humans. European Journal of Pharmaceutical Sciences, 41(5):729-735.

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Abstract

Garlic extracts have been shown to decrease drug exposure for saquinavir, a P-glycoprotein and cytochrome P450 3A4 substrate. In order to explore the underlying mechanisms and to study the effects of garlic on pre-systemic drug elimination, healthy volunteers were administered garlic extract for 21 days. Prior to and at the end of this period, expression of duodenal P-glycoprotein and cytochrome P450 3A4 protein were assayed and normalized to villin, while hepatic cytochrome P450 3A4 function and simvastatin, pravastatin and saquinavir pharmacokinetics were also evaluated. Ingestion of garlic extract increased expression of duodenal P-glycoprotein to 131% (95% CI, 105-163%), without increasing the expression of cytochrome P450 3A4 which amounted to 87% (95% CI, 67-112%), relative to baseline in both cases. For the erythromycin breath test performed, the average result was 96% (95% CI, 83-112%). Ingestion of garlic extract had no effect on drug and metabolite AUCs following a single dose of simvastatin or pravastatin, although the average area under the plasma concentration curve (AUC) of saquinavir decreased to 85% (95% CI, 66-109%), and changes in intestinal P-glycoprotein expression negatively correlated with this change. In conclusion, garlic extract induces intestinal expression of P-glycoprotein independent of cytochrome P450 3A4 in human intestine and liver.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Clinical Chemistry
04 Faculty of Medicine > University Hospital Zurich > Clinic for Nuclear Medicine
04 Faculty of Medicine > University Hospital Zurich > Clinic for Clinical Pharmacology and Toxicology
DDC:610 Medicine & health
540 Chemistry
Language:English
Date:2010
Deposited On:18 Jan 2011 14:27
Last Modified:27 Nov 2013 18:00
Publisher:Elsevier
ISSN:0928-0987
Publisher DOI:10.1016/j.ejps.2010.09.016
PubMed ID:20933082
Citations:Web of Science®. Times Cited: 14
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Scopus®. Citation Count: 22

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