| Isolation and identification of intestinal CYP3A inhibitors from cranberry (Vaccinium macrocarpon) using human intestinal microsomes. | |
| | |
MedLine Citation:
|
PMID: 20717876 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Cranberry juice is used routinely, especially among women and the elderly, to prevent and treat urinary tract infections. These individuals are likely to be taking medications concomitantly with cranberry juice, leading to concern about potential drug-dietary substance interactions, particularly in the intestine, which, along with the liver, is rich in expression of the prominent drug metabolizing enzyme, cytochrome P450 3A (CYP3A). Using a systematic in vitro-in vivo approach, a cranberry juice product was identified recently that elicited a pharmacokinetic interaction with the CYP3A probe substrate midazolam in 16 healthy volunteers. Relative to water, cranberry juice inhibited intestinal first-pass midazolam metabolism. In vitro studies were initiated to identify potential enteric CYP3A inhibitors from cranberry via a bioactivity-directed fractionation approach involving dried whole cranberry [Vaccinium macrocarpon Ait. (Ericaceae)], midazolam, and human intestinal microsomes (HIM). Three triterpenes (maslinic acid, corosolic acid, and ursolic acid) were isolated. The inhibitory potency (IC(50)) of maslinic acid, corosolic acid, and ursolic acid was 7.4, 8.8, and < 10 µM, respectively, using HIM as the enzyme source and 2.8, 4.3, and < 10 µM, respectively, using recombinant CYP3A4 as the enzyme source. These in vitro inhibitory potencies, which are within the range of those reported for two CYP3A inhibitory components in grapefruit juice, suggest that these triterpenes may have contributed to the midazolam-cranberry juice interaction observed in the clinical study. |
| | |
Authors:
|
Eunkyung Kim; Arlene Sy-Cordero; Tyler N Graf; Scott J Brantley; Mary F Paine; Nicholas H Oberlies |
Related Documents
:
|
12060866 - Comparison of inhibitory activity on calcium phosphate precipitation by acidic proline-... 3297476 - Occurrence, absorption and metabolism of short chain fatty acids in the digestive tract... 7275886 - Lead in preserved duck eggs: field screening test and confirmation and quantitation by ... 2632246 - Benefit vs. risk of oral aluminum forms: antacid and phosphate binding vs. absorption. 16233496 - Two o-methyltransferases isolated from flower petals of rosa chinensis var. spontanea i... 16232686 - Formulation of defined media for carbon monoxide fermentation by eubacterium limosum ki... |
Publication Detail:
|
Type: Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-08-17 |
Journal Detail:
|
Title: Planta medica Volume: 77 ISSN: 1439-0221 ISO Abbreviation: Planta Med. Publication Date: 2011 Feb |
Date Detail:
|
Created Date: 2011-02-09 Completed Date: 2011-09-26 Revised Date: 2012-02-02 |
Medline Journal Info:
|
Nlm Unique ID: 0066751 Medline TA: Planta Med Country: Germany |
Other Details:
|
Languages: eng Pagination: 265-70 Citation Subset: IM |
Copyright Information:
|
© Georg Thieme Verlag KG Stuttgart · New York. |
Affiliation:
|
Herbal Medicinal Products Division, Korea Food and Drug Administration, Seoul, Republic of Korea. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Beverages Cytochrome P-450 CYP3A / antagonists & inhibitors* Enzyme Inhibitors / pharmacology Food-Drug Interactions* Fruit Humans Intestines / drug effects*, enzymology Microsomes / drug effects Midazolam / metabolism* Plant Extracts / chemistry, pharmacology* Recombinant Proteins Triterpenes / isolation & purification, pharmacology* Vaccinium macrocarpon / chemistry* |
| Grant Support | |
ID/Acronym/Agency:
|
R01 GM077482/GM/NIGMS NIH HHS; R01 GM077482-01A2/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Enzyme Inhibitors; 0/Plant Extracts; 0/Recombinant Proteins; 0/Triterpenes; 59467-70-8/Midazolam; EC 1.14.14.1/Cytochrome P-450 CYP3A |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Clinical Evaluation of Efficacy and Tolerability of HMC05 in Healthy Subjects with Normal and High-N...
Next Document: Inhibition of advanced glycation end product formation by medicinal plant extracts correlates with p...