Document Detail


The inhibitory effect of oral contraceptives on CYP2C19 activity is not significant in carriers of the CYP2C19*17 allele.
MedLine Citation:
PMID:  23844835     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The purpose of the study was to examine if Cytochrome P450 2C19 (CYP2C19) in carriers of the CYP2C19*17 allele is inhibited in vivo by oral contraceptives (OC). Retrospective CYP2C19 phenotyping by omeprazole/5-OH-omeprazole molar 3-hour plasma metabolic ratios (MR) from a population (n=222) genotyped as CYP2C19*1/*1, CYP2C19*1/*17 and CYP2C19*17/*17 were analysed. Furthermore, 30 women genotyped as CYP2C19*1/*1 (n=11), CYP2C19*1/*17 (n=11) and CYP2C19*17/*17 (n=8) were prospectively CYP2C19 phenotyped during the administration of OC and again after a minimum of five days break from OC. We found a statistically significantly higher MR in the CYP2C19*1/*1 genotype group that took OC (n=48) compared to the women that did not take OC (n=31) (geometric mean of 1.37 vs. 0.83, p<0.05). However, in the CYP2C19*1/*17 genotype group, the geometric means of the MR in 37 taking OC and in 20 not taking OC were 0.67 and 0.46, respectively (p>0.05). In the CYP2C19*1/*1 panel of the prospective cross-over study, we also found a statistically significantly higher MR during OC compared to the MR in the OC break (geometric means of 1.21 vs. 0.91, respectively, p=0.0123). However, in the CYP2C19*1/*17, the geometric means of the MR were 0.77 with OC and 0.65 without OC, and the corresponding values in the CYP2C19*17/*17 were 1.05 and 0.79 (p=0.20 and 0.17, respectively). In conclusion, we showed that OC intake inhibits CYP2C19 in homozygous carriers of the CYP2C19 wildtype but that the inhibition is not statistically significant in the heterozygous and in the homozygous carriers of the CYP2C19*17 allele. This article is protected by copyright. All rights reserved.
Authors:
Rasmus Steen Pedersen; Lene Noehr-Jensen; Kim Brosen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-7-11
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  -     ISSN:  1440-1681     ISO Abbreviation:  Clin. Exp. Pharmacol. Physiol.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-7-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
This article is protected by copyright. All rights reserved.
Affiliation:
Institute of Public Health, Clinical Pharmacology, University of Southern Denmark, Odense, Denmark.
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