ArticleEuropean journal of drug metabolism and pharmacokinetics2017
Evaluation of In Vitro Cytochrome P450 Inhibition and In Vitro Fate of Structurally Diverse N-Oxide Metabolites: Case Studies with Clozapine, Levofloxacin, Roflumilast, Voriconazole and Zopiclone.
Article in European journal of drug metabolism and pharmacokinetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 20 citations in OpenAlex.
- Roles of selected non-P450 human oxidoreductase enzymes in protective and toxic effects of chemicals: review and compilation of reactions.Archives of toxicology · 2022Review
- Towards the Elucidation of the Pharmacokinetics of Voriconazole: A Quantitative Characterization of Its Metabolism.Pharmaceutics · 2022Article
- Efficacy, Safety, and Drug-Drug Interactions for Insomnia Therapy in COVID-19 Patients.Journal of multidisciplinary healthcare · 2022Review
- Physiologically Based Pharmacokinetic Modeling of Bupropion and Its Metabolites in a CYP2B6 Drug-Drug-Gene Interaction Network.Pharmaceutics · 2021Article
- Predictors of Adverse Events and Determinants of the Voriconazole Trough Concentration in Kidney Transplantation Recipients.Clinical and translational science · 2021Observational
- Inhibition of Hepatic CYP2D6 by the Active N-Oxide Metabolite of Sorafenib.The AAPS journal · 2019Article
- Sorafenib N-Oxide Is an Inhibitor of Human Hepatic CYP3A4.The AAPS journal · 2019Article
- PharmGKB summary: clozapine pathway, pharmacokinetics.Pharmacogenetics and genomics · 2018Article
- In Vitro Drug-Drug Interaction Potential of Sulfoxide and/or Sulfone Metabolites of Albendazole, Triclabendazole , Aldicarb, Methiocarb, Montelukast and Ziprasidone.Drug metabolism letters · 2018Article
- The Role of Drug Metabolites in the Inhibition of Cytochrome P450 Enzymes.European journal of drug metabolism and pharmacokinetics · 2017Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesThe role of metabolite(s) to elicit potential clinical drug-drug interaction (DDI) via cytochrome P450 enzymes (CYP) is gaining momentum. In this context, the role of N-oxides for in vitro CYP inhibition has not been evaluated. The objectives of this study were: (a) to examine in vitro CYP inhibition of N-oxides of clozapine, levofloxacin, roflumilast, voriconazole and zopiclone in a tiered approach and (b) evaluate in vitro fate of aforementioned N-oxides examined in recombinant CYPs, human microsomes and hepatocytes.
methodsCYP enzymes evaluated in the work included: CYP1A2, 2B6, 2C9, 2C19, 2D6 and 3A4 using standard procedures for incubation with appropriate probe substrates. The initial cutoff for CYP inhibition was ≥50% using 2 and 10 µM concentrations of various N-oxide metabolites (Tier 1). IC
resultsN-oxides of clozapine (CYP2B6/2C19) and voriconazole (CYP2C9/3A4) showed CYP inhibition ≥50%. Clozapine-N-oxide inhibited CYP2B6 and CYP2C19 pathways with IC
conclusionsClinical DDI potential of specific CYP enzymes needs to be considered arising due to circulatory concentrations of certain N-oxides depending on the dose size and/or frequency of dosing of the respective parent drugs.
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