Pharmacokinetics of midazolam in CYP3A4- and CYP3A5-genotyped subjects
Details
State: Public
Version: Final published version
License: Not specified
It was possible to publish this article open access thanks to a Swiss National Licence with the publisher.
Serval ID
serval:BIB_C414875FF528
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Pharmacokinetics of midazolam in CYP3A4- and CYP3A5-genotyped subjects
Journal
European journal of clinical pharmacology
ISSN
0031-6970
Publication state
Published
Issued date
2004
Peer-reviewed
Oui
Volume
60
Number
4
Pages
231-236
Language
english
Notes
Publication types: Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
OBJECTIVE: We investigated whether differences in pharmacokinetics of midazolam, a CYP3A probe, could be demonstrated between subjects with different CYP3A4 and CYP3A5 genotypes. METHODS: Plasma concentrations of midazolam, and of total (conjugated + unconjugated) 1'OH-midazolam, and 4'OH-midazolam were measured after the oral administration of 7.5 mg or of 75 micro g of midazolam in 21 healthy subjects. RESULTS: CYP3A5*7, CYP3A4*1E, CYP3A4*2, CYP3A4*4, CYP3A4*5, CYP3A4*6, CYP3A4*8, CYP3A4*11, CYP3A4*12, CYP3A4*13, CYP3A4*17 and CYP3A4*18 alleles were not identified in the 21 subjects. CYP3A5*3, CYP3A5*6, CYP3A4*1B and CYP3A4*1F alleles were identified in 20, 1, 4 and 2 subjects, respectively. No statistically significant differences were observed for the AUC(inf) values between the different genotypes after the 75- micro g or the 7.5-mg dose. CONCLUSION: Presently, CYP3A4 and CYP3A5 genotyping methods do not sufficiently reflect the inter-individual variability of CYP3A activity.
Keywords
Area Under Curve, Cytochrome P-450 CYP3A, Cytochrome P-450 Enzyme System, Female, Genotype, Humans, Male, Midazolam
Pubmed
Web of science
Open Access
Yes
Create date
10/03/2008 11:54
Last modification date
14/02/2022 8:57
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