Oral administration of a low dose of midazolam (75 microg) as an in vivo probe for CYP3A activity.
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_9381D46D9A28
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Oral administration of a low dose of midazolam (75 microg) as an in vivo probe for CYP3A activity.
Journal
European journal of clinical pharmacology
ISSN
0031-6970
Publication state
Published
Issued date
2004
Peer-reviewed
Oui
Volume
60
Number
4
Pages
237-46
Language
english
Notes
Publication types: Clinical Trial ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
OBJECTIVE: We investigated whether the oral administration of a low dose (75 micro g) of midazolam, a CYP3A probe, can be used to measure the in vivo CYP3A activity. METHODS: Plasma concentrations of midazolam, 1'OH-midazolam and 4'OH-midazolam were measured after the oral administration of 7.5 mg and 75 micro g midazolam in 13 healthy subjects without medication, in four subjects pretreated for 2 days with ketoconazole (200 mg b.i.d.), a CYP3A inhibitor, and in four subjects pretreated for 4 days with rifampicin (450 mg q.d.), a CYP3A inducer. RESULTS: After oral administration of 75 micro g midazolam, the 30-min total (unconjugated + conjugated) 1'OH-midazolam/midazolam ratios measured in the groups without co-medication, with ketoconazole and with rifampicin were (mean+/-SD): 6.23+/-2.61, 0.79+/-0.39 and 56.1+/-12.4, respectively. No side effects were reported by the subjects taking this low dose of midazolam. Good correlations were observed between the 30-min total 1'OH-midazolam/midazolam ratio and midazolam clearance in the group without co-medication (r(2)=0.64, P<0.001) and in the three groups taken together (r(2)=0.91, P<0.0001). Good correlations were also observed between midazolam plasma levels and midazolam clearance, measured between 1.5 h and 4 h. CONCLUSION: A low oral dose of midazolam can be used to phenotype CYP3A, either by the determination of total 1'OH-midazolam/midazolam ratios at 30 min or by the determination of midazolam plasma levels between 1.5 h and 4 h after its administration.
Keywords
Adult, Aryl Hydrocarbon Hydroxylases, Cross-Over Studies, Cytochrome P-450 CYP3A, Dose-Response Relationship, Drug, Enzyme Induction, Female, Humans, Ketoconazole, Male, Midazolam, Middle Aged, Oxidoreductases, N-Demethylating
Pubmed
Web of science
Open Access
Yes
Create date
10/03/2008 10:38
Last modification date
14/02/2022 7:56