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Inhibitory effect of oral contraceptives on CYP2C19 activity is not significant in carriers of the CYP2C19 * 17 allele
Author(s) -
Pedersen Rasmus S.,
NoehrJensen Lene,
Brosen Kim
Publication year - 2013
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12153
Subject(s) - cyp2c19 , omeprazole , allele , genotype , medicine , population , endocrinology , pharmacology , chemistry , cytochrome p450 , metabolism , biochemistry , gene , environmental health
Summary The purpose of the present study was to examine whether cytochrome P450 2C19 ( CYP 2C19) in carriers of the CYP2C19 * 17 allele is inhibited in vivo by oral contraceptives ( OC ). Retrospective CYP 2C19 phenotyping according to omeprazole : 5‐ OH ‐omeprazole molar 3 h plasma metabolic ratios ( MR ) from a population ( n = 222) genotyped as CYP2C19 * 1/ * 1 , CYP2C19 * 1/ * 17 and CYP2C19 * 17/ * 17 was analysed. Furthermore, 30 women genotyped as CYP2C19 * 1/ * 1 ( n = 11), CYP2C19 * 1/ * 17 ( n = 11) and CYP2C19 * 17/ * 17 ( n = 8) were prospectively CYP 2C19 phenotyped during the administration of OC and again after a minimum 5 days break from OC . We found a significantly higher MR in the CYP 2C19 * 1/ * 1 genotype group that took OC ( n = 48) compared with women who did not take OC ( n = 31; geometric mean 1.37 vs 0.83, respectively; P < 0.05). However, in the CYP2C19 * 1/ * 17 genotype group, the geometric means of the MR in the 37 women taking OC and the 20 women 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 found a significantly higher MR while women were taking the OC compared with the MR during the OC break (geometric mean 1.21 vs 0.91, respectively; P = 0.0123). However, in the CYP2C19 * 1/ * 17 group, the geometric means of the MR with and without OC were 0.77 and 0.65, respectively, compared with 1.05 and 0.79, respectively, in the CYP 2C19 * 17/ * 17 group ( P = 0.20 and 0.17, respectively). In conclusion, we have shown that OC intake inhibits CYP 2C19 in homozygous carriers of the CYP2C19 wild type but that the inhibition is not significant in heterozygous and homozygous carriers of the CYP2C19 * 17 allele.