In vitro inhibition of midazolam and quinidine metabolism by flavonoids

Details

Serval ID
serval:BIB_B22436748361
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
In vitro inhibition of midazolam and quinidine metabolism by flavonoids
Journal
European Journal of Clinical Pharmacology
Author(s)
Ha  H. R., Chen  J., Leuenberger  P. M., Freiburghaus  A. U., Follath  F.
ISSN
0031-6970 (Print)
Publication state
Published
Issued date
1995
Volume
48
Number
5
Pages
367-71
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Abstract
Studies in humans in vivo have demonstrated that substances found in grapefruit juice may increase the bioavailability of dihydropyridine derivatives as a result of the inhibition of liver enzyme activities by flavonoids found in grapefruit. Since the metabolism of dihydropyridine drugs is mediated by cytochrome P-450 (CYP) 3A4, it has been hypothesized that flavonoids may also influence the metabolism of other drugs, such as midazolam and quinidine, which are biotransformed by the same CYP isoform. Three flavonoids, kaempferol, naringenin and quercetin, are found in grapefruit juice but not in orange juice. The effect of these substances on the metabolism of midazolam and quinidine has been investigated in human liver microsomes. In the concentration range 10-160 microM the inhibitory potential of flavonoids was the same for both of the tested drugs; it decreased in the order quercetin >> kaempferol > naringenin. The data suggest that the flavonoids found in grapefruit juice may influence the kinetics of midazolam and quinidine in man.
Keywords
Anti-Arrhythmia Agents/antagonists & inhibitors/*metabolism Cytochrome P-450 Enzyme System/antagonists & inhibitors/metabolism Drug Interactions Enzyme Inhibitors/*pharmacology Flavonoids/*pharmacology Humans Kinetics Midazolam/analogs & derivatives/antagonists & inhibitors/*metabolism Mixed Function Oxygenases/antagonists & inhibitors/metabolism Quinidine/analogs & derivatives/antagonists & inhibitors/*metabolism
Pubmed
Web of science
Create date
25/01/2008 10:50
Last modification date
20/08/2019 16:20
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