Effect of sex and menstrual cycle phase on cytochrome P450 2C19 activity with omeprazole used as a biomarker
Bibliographic record
Abstract
BACKGROUND: Literature addressing the effect of sex on cytochrome P450 (CYP) 2C19 activity is conflicting. The exogenous female sex steroid hormones used in oral contraceptives are believed to significantly inhibit CYP2C19 activity. However, the effect of variations in endogenous sex steroid concentrations throughout the menstrual cycle has not been investigated. OBJECTIVE: The objective of this study was to determine the effects of sex and menstrual cycle phase on CYP2C19 activity by using omeprazole. METHODS: White subjects with body weights between 45 and 66 kg received a single oral dose of 30 mg omeprazole. Those with weights of 67 to 90 kg received a dose of 40 mg. Twelve female subjects were phenotyped during the midfollicular and midluteal phases of the menstrual cycle for 3 complete cycles. Twelve male subjects were phenotyped every 14 days for 12 weeks. The 2-hour postdose plasma concentration ratio of omeprazole to 5'-hydroxyomeprazole was used as a measure of CYP2C19 activity. All subjects were genotyped for CYP2C19*2 and *3 alleles. RESULTS: Twelve women and 8 men were extensive metabolizers (EMs) with a CYP2C19*1/*1 genotype, whereas 4 male subjects were heterozygous (CYP2C19*1/*2). Median metabolic ratios during the midfollicular and midluteal visits were 0.845 and 0.930, respectively (P =.7). Sex had no effect on CYP2C19 activity in CYP2C19*1/*1 EMs (0.875 for men versus 1.070 for women, P =.140). The median metabolic ratios of all individuals with 2C19*1/*1 and *1/*2 genotypes were 0.94 and 3.75, respectively. CONCLUSION: 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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".