ArticleEuropean journal of clinical pharmacology2022
Evaluation of CYP2C19 activity using microdosed oral omeprazole in humans.
Article in European journal of clinical pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 7 citations in OpenAlex.
- Time Course of the Interaction Between Oral Short-Term Ritonavir Therapy with Three Factor Xa Inhibitors and the Activity of CYP2D6, CYP2C19, and CYP3A4 in Healthy Volunteers.Clinical pharmacokinetics · 2024Trial
- Search for Novel Biomarkers to Predict Cytochrome P450 2C19 Activity Using Untargeted Metabolomics of Human Plasma.Metabolites · 2026Article
- An Evaluation of the Drug Interaction Potential of Encorafenib in Combination With Binimetinib Using the Inje Cocktail in Patients With Cancer.Clinical pharmacology and therapeutics · 2026Article
- Development and validation of a clinical-pharmacogenomic prediction model for clopidogrel-related high on-treatment platelet reactivity in patients with coronary artery disease.Frontiers in cardiovascular medicine · 2026Article
- Article
- Drug interaction potential of high-dose rifampicin in patients with pulmonary tuberculosis.Antimicrobial agents and chemotherapy · 2023Article
- CYP3A and CYP2C19 Activity Determined by Microdosed Probe Drugs Accurately Predict Voriconazole Clearance in Healthy Adults.Clinical pharmacokinetics · 2023Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo investigate the suitability of microdosed oral omeprazole for predicting CYP2C19 activity in vivo in combination with simultaneous assessment of CYP3A and CYP2D6 activity using both microdosed midazolam and yohimbine.
methodsAn open, fixed-sequence study was carried out in 20 healthy participants. Single microdosed (100 µg) and therapeutic (20 mg) doses of omeprazole were evaluated without comedication and after administration of established CYP2C19 perpetrators fluconazole (inhibition) and rifampicin (induction). To prevent degradation of the uncoated omeprazole microdose, sodium bicarbonate buffer was administered. The pharmacokinetics of omeprazole and its 5-hydroxy-metabolite were assessed as well as the pharmacokinetics of midazolam and yohimbine to estimate CYP3A4 and CYP2D6 activity.
resultsCalculated pharmacokinetic parameters after administration of 100 µg and 20 mg omeprazole in healthy subjects suggest dose proportionality. Omeprazole clearance was significantly decreased by fluconazole from 388 [95% CI: 266-565] to 47.2 [42.8-52.0] mL/min after 20 mg omeprazole and even further after 100 µg omeprazole (29.4 [24.5-35.1] mL/min). Rifampicin increased CYP2C19-mediated omeprazole metabolism. The omeprazole hydroxylation index was significantly related to omeprazole clearance for both doses. Both fluconazole and rifampicin altered CYP3A4 activity whereas no change of CYP2D6 activity was observed at all.
conclusionsMicrodosed oral omeprazole is suitable to determine CYP2C19 activity, also during enzyme inhibition and induction. However, the administration of sodium bicarbonate buffer also had a small influence on all victim drugs used.
trial registrationEudraCT: 2017-004270-34.
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