CYP3A activity measured by the midazolam test is not related to 3435 C >T polymorphism in the multiple drug resistance transporter gene.

Details

Serval ID
serval:BIB_0DA344954504
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
CYP3A activity measured by the midazolam test is not related to 3435 C >T polymorphism in the multiple drug resistance transporter gene.
Journal
Pharmacogenetics
Author(s)
Eap C.B., Fellay J., Buclin T., Bleiber G., Golay K.P., Brocard M., Baumann P., Telenti A.
ISSN
0960-314X (Print)
ISSN-L
0960-314X
Publication state
Published
Issued date
2004
Peer-reviewed
Oui
Volume
14
Number
4
Pages
255-260
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
A recent study with 69 Japanese liver transplants treated with tacrolimus found that the MDR13435 C >T polymorphism, but not the MDR12677 G >T polymorphism, was associated with differences in the intestinal expression level of CYP3A4 mRNA. In the present study, over 6 h, we measured the kinetics of a 75 microg oral dose of midazolam, a CYP3A substrate, in 21 healthy subjects genotyped for the MDR13435 C >T and 2677 G >T polymorphism. No statistically significant differences were found in the calculated pharmacokinetic parameters between the three 3435 C >T genotypes (TT, CT and CC group, respectively: Cmax (mean +/- SD: 0.30 +/- 0.08 ng/ml, 0.31 +/- 0.09 ng/ml and 0.31 +/- 0.11 ng/ml; Apparent clearance: 122 +/- 29 l/h, 156 +/- 92 l/h and 111 +/- 35 l/h; t1/2: 1.9 +/- 1.1 h, 1.6 +/- 0.90 h and 1.7 +/- 0.7 h). In addition, the 30-min 1'OH midazolam to midazolam ratio, a marker of CYP3A activity, determined in 74 HIV-positive patients before the introduction of antiretroviral treatment, was not significantly different between the three 3435 C >T genotypes (mean ratio +/- SD: 3.65 +/- 2.24, 4.22 +/- 3.49 and 4.24 +/- 2.03, in the TT, CT and CC groups, respectively). Similarly, no association was found between the MDR12677 G >T polymorphism and CYP3A activity in the healthy subjects or in the HIV-positive patients. The existence of a strong association between the activity of CYP3A and MDR13435 C >T and 2677 G >T polymorphisms appears unlikely, at least in Caucasian populations and/or in the absence of specific environmental factors.
Keywords
Adult, Base Sequence, Cytochrome P-450 CYP3A, Cytochrome P-450 Enzyme System/genetics, Cytochrome P-450 Enzyme System/metabolism, DNA Primers, Female, Humans, Male, Midazolam/pharmacokinetics, Midazolam/pharmacology, Middle Aged, P-Glycoprotein/genetics, Polymorphism, Genetic, RNA, Messenger/genetics
Pubmed
Web of science
Create date
10/03/2008 10:54
Last modification date
20/08/2019 12:34
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