Effect of sex and menstrual cycle phase on cytochrome P450 2C19 activity with omeprazole used as a biomarker

Abstract

There is no sex difference in CYP2C19 activity in healthy white CYP2C19*1/*1 EMs with the omeprazole ratios. A gene-dose effect was observed. In addition, variations in endogenous sex steroid concentrations throughout the menstrual cycle did not influence CYP2C19 activity.

Analysis of omeprazole, midazolam and hydroxy-metabolites in plasma using liquid chromatography coupled to tandem mass spectrometry

“…Omeprazole has the advantages of easy administration, the potential for single point measurement of the HI, and an excellent safety profile. Disadvantages of OPZ for CYP2C19 phenotyping include a high degree of intrasubject variability reported with the 2 h index [14], and a portion of subjects having undetectable parent or metabolite serum concentrations at the single point sampling time [3,14]. Use of a larger oral dose or use of AUC ratios may overcome the limitation of undetectable serum concentrations with single point methods, as well as better analytical methods.…”

“…Oral mephenytoin, the preferred probe substrate in the past, is no longer available and has a risk of sedative adverse effects, especially in poor metabolizers [11]. The ratio of serum OPZ to 5 -hydroxyomeprazole (OH-OPZ) concentrations, also called the hydroxylation index (HI) has excellent concordance with CYP2C19 genotype [11][12][13], and is not influenced by gender or menstrual cycle phase [14]. In addition, the omeprazole HI is normally distributed among extensive metabolizers, potentially allowing more detailed studies within this group.…”

Use of Omeprazole as a CYP3A Probe Drug: Effect of Sex and Menstrual Cycle Phase on CYP3A Activity in Healthy Caucasian Adults

“…32 The current study attempted to address whether sex or menstrual cycle differences in CYP3A activity, as determined by the omeprazole sulphone pathway, exist. Omeprazole meets most of the compulsory criteria that are proposed to validate a probe based on tests of a drugmetabolizing enzyme.…”

The Menstrual Cycle and Drug Metabolism

“…The majority of these occurred when investigating cytochrome P4502D6, presumably as the expression of metabolic capacity in the form of metabolic ratios has become almost ingrained and automatic for this polymorphic isoform. Two instances where differences have been observed in measured metabolism have been for the aforementioned cytochrome P4502D6 with debrisoquine [74] and cytochrome P4503A4 with midazolam [87].…”