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

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

Eap, Chin B.
•
Fellay, Jacques  
•
Buclin, Thierry
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2004
Pharmacogenetics

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.

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Type
research article
DOI
10.1097/00008571-200404000-00005
Author(s)
Eap, Chin B.
•
Fellay, Jacques  
•
Buclin, Thierry
•
Bleiber, Gabriela
•
Golay, Kerry Powell
•
Brocard, Murielle
•
Baumann, Pierre
•
Telenti, Amalio
Date Issued

2004

Published in
Pharmacogenetics
Volume

14

Issue

4

Start page

255

End page

60

Subjects

Polymorphism, Genetic

Peer reviewed

REVIEWED

Written at

OTHER

EPFL units
UPFELLAY  
Available on Infoscience
April 15, 2011
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/66456
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