ArticleDrug metabolism and disposition: the biological fate of chemicals2013
Inhibition of CYP2C19 and CYP3A4 by omeprazole metabolites and their contribution to drug-drug interactions.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- Pharmacokinetic Drug-Drug Interactions of Imlunestrant in Healthy Female Participants of Nonchildbearing Potential.Clinical and translational science · 2026Pooled it
- An Open Label, Phase 1, Randomized, Seven-treatment, Seven-period, Crossover Study to Assess the Relative Bioavailability, pH Effect, Food Effect, and Dose Proportionality of CC-292, a Potent and Orally Available Bruton's Tyrosine Kinase Inhibitor.European journal of drug metabolism and pharmacokinetics · 2022Trial
- Effects of proton pump inhibitors, esomeprazole and vonoprazan, on the disposition of proguanil, a CYP2C19 substrate, in healthy volunteers.British journal of clinical pharmacology · 2019Trial
- Use of a cocktail probe to assess potential drug interactions with cytochrome P450 after administration of belatacept, a costimulatory immunomodulator.British journal of clinical pharmacology · 2017Trial
- An S-warfarin and AZD1981 interaction: in vitro and clinical pilot data suggest the N-deacetylated amino acid metabolite as the primary perpetrator.British journal of clinical pharmacology · 2017Trial
- Model-Based Virtual Clinical Trial Reveals Renal Impairment and Body Size as Key Determinants of Pharmacokinetic Variability and Drug-Drug Interaction Risk in Propranolol Therapy.Pharmaceutics · 2026Article
- Role of metabolites in drug-drug interactions.Drug metabolism and pharmacokinetics · 2026Review
- The administration of proton pump inhibitors with the CDK4/6 inhibitor abemaciclib does not affect the clinical outcome of metastatic breast cancer patients.Therapeutic advances in drug safety · 2026Article
- A complementary dual-platform analytical strategy for resolving matrix effects and stability limitations in bioanalysis.Frontiers in veterinary science · 2026Article
- Burden and Determinants of Drug-Drug Interactions at Hospital Discharge: Warfarin as a Model for High-Risk Medication Safety.Clinics and practice · 2025Article
- Dermatomyositis, Rhabdomyolysis, and Statin-Induced Myopathy: A Case Report Illustrating the Spectrum of Myopathy.Cureus · 2025Article
- Leveraging Omeprazole PBPK/PD Modeling to Inform Drug-Drug Interactions and Specific Recommendations for Pediatric Labeling.Pharmaceutics · 2025Article
- Risk of Proton Pump Inhibitor (PPI)-Induced Galactorrhea: An Uncommon Adverse Effect of a Common Drug.Cureus · 2025Article
- Article
- Pharmacotherapy variability and precision medicine in neurocritical care.Frontiers in neurology · 2025Review
- Isolation, Structure Elucidation, and Bioactivity Evaluation of Two Alkaloids FromFood science & nutrition · 2024Article
- Impact of obesity and roux-en-Y gastric bypass on the pharmacokinetics of (R)- and (S)-omeprazole and intragastric pH.CPT: pharmacometrics & systems pharmacology · 2024Article
- The Effect of Concomitant Administration of Proton Pump Inhibitors on the Pharmacokinetics of CDK4/6 Inhibitors in Rats: Implications for the Evaluation of Hepatic and Transporter-Mediated Drug-Drug Interactions.European journal of drug metabolism and pharmacokinetics · 2024Article
- Suspected Hematuria: Adverse Effects of Rivaroxaban in Older Adult Treated for Atrial Fibrillation.Reports (MDPI) · 2024Article
- Use of physiologically-based pharmacokinetic modeling to understand the effect of omeprazole administration on the pharmacokinetics of oral extended-release nifedipine.CPT: pharmacometrics & systems pharmacology · 2024Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The aim of this study was to evaluate the contribution of metabolites to drug-drug interactions (DDI) using the inhibition of CYP2C19 and CYP3A4 by omeprazole and its metabolites as a model. Of the metabolites identified in vivo, 5-hydroxyomeprazole, 5'-O-desmethylomeprazole, omeprazole sulfone, and carboxyomeprazole had a metabolite to parent area under the plasma concentration-time curve (AUC(m)/AUC(p)) ratio ≥ 0.25 when either total or unbound concentrations were measured after a single 20-mg dose of omeprazole in a cocktail. All of the metabolites inhibited CYP2C19 and CYP3A4 reversibly. In addition omeprazole, omeprazole sulfone, and 5'-O-desmethylomeprazole were time dependent inhibitors (TDI) of CYP2C19, whereas omeprazole and 5'-O-desmethylomeprazole were found to be TDIs of CYP3A4. The in vitro inhibition constants and in vivo plasma concentrations were used to evaluate whether characterization of the metabolites affected DDI risk assessment. Identifying omeprazole as a TDI of both CYP2C19 and CYP3A4 was the most important factor in DDI risk assessment. Consideration of reversible inhibition by omeprazole and its metabolites would not identify DDI risk with CYP3A4, and with CYP2C19, reversible inhibition values would only identify DDI risk if the metabolites were included in the assessment. On the basis of inactivation data, CYP2C19 and CYP3A4 inhibition by omeprazole would be sufficient to identify risk, but metabolites were predicted to contribute 30-63% to the in vivo hepatic interactions. Therefore, consideration of metabolites may be important in quantitative predictions of in vivo DDIs. The results of this study show that, although metabolites contribute to in vivo DDIs, their relative abundance in circulation or logP values do not predict their contribution to in vivo DDI risk.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.