TY - JOUR
T1 - Inhibitory effect of oral contraceptives on CYP2C19 activity is not significant in carriers of the CYP2C19*17 allele
AU - Pedersen, Rasmus S
AU - Noehr-Jensen, Lene
AU - Brosen, Kim
PY - 2013/10
Y1 - 2013/10
N2 - (1) The purpose of the present study was to examine whether cytochrome P450 2C19 (CYP2C19) in carriers of the CYP2C19*17 allele is inhibited in vivo by oral contraceptives (OC). (2) Retrospective CYP2C19 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 CYP2C19 phenotyped during the administration of OC and again after a minimum 5 days break from OC. (3) We found a significantly higher MR in the CYP2C19*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 CYP2C19*17/*17 group (P = 0.20 and 0.17, respectively). (4) In conclusion, we have shown that OC intake inhibits CYP2C19 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.
AB - (1) The purpose of the present study was to examine whether cytochrome P450 2C19 (CYP2C19) in carriers of the CYP2C19*17 allele is inhibited in vivo by oral contraceptives (OC). (2) Retrospective CYP2C19 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 CYP2C19 phenotyped during the administration of OC and again after a minimum 5 days break from OC. (3) We found a significantly higher MR in the CYP2C19*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 CYP2C19*17/*17 group (P = 0.20 and 0.17, respectively). (4) In conclusion, we have shown that OC intake inhibits CYP2C19 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.
KW - 2-Pyridinylmethylsulfinylbenzimidazoles
KW - Adult
KW - Alleles
KW - Aryl Hydrocarbon Hydroxylases
KW - Contraceptives, Oral
KW - Cytochrome P-450 CYP2C19
KW - Female
KW - Gene Expression
KW - Genotype
KW - Heterozygote
KW - Humans
KW - Journal Article
KW - Middle Aged
KW - Mutation
KW - Omeprazole
KW - Proton Pump Inhibitors
KW - Research Support, Non-U.S. Gov't
KW - Young Adult
U2 - 10.1111/1440-1681.12153
DO - 10.1111/1440-1681.12153
M3 - Journal article
C2 - 23844835
SN - 0305-1870
VL - 40
SP - 683
EP - 688
JO - Clinical and Experimental Pharmacology and Physiology
JF - Clinical and Experimental Pharmacology and Physiology
IS - 10
ER -