ArticleBiochemical pharmacology2014
Investigating the contribution of CYP2J2 to ritonavir metabolism in vitro and in vivo.
Article in Biochemical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation Approaches: A Systematic Review of Published Models, Applications, and Model Verification.Drug metabolism and disposition: the biological fate of chemicals · 2015Pooled it
- 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
- The Hunt for the Putative Epoxyeicosatrienoic Acid Receptor.ACS chemical biology · 2025Review
- Construction of a CYP2J2-Template System and Its Application for Ligand Metabolism Prediction.Food safety (Tokyo, Japan) · 2024Article
- Potential herb‒drug interactions between anti-COVID-19 drugs and traditional Chinese medicine.Acta pharmaceutica Sinica. B · 2023Review
- Characterization of 15 CYP2J2 variants identified in the Chinese Han population on the metabolism of ebastine and terfenadineFrontiers in pharmacology · 2023Article
- Physiologically-Based Pharmacokinetic Modeling-Guided Dose Management of Oral Anticoagulants when Initiating Nirmatrelvir/Ritonavir (Paxlovid) for COVID-19 Treatment.Clinical pharmacology and therapeutics · 2022Article
- The Mechanism-Based Inactivation of CYP3A4 by Ritonavir: What Mechanism?International journal of molecular sciences · 2022Review
- Development of ritonavir-loaded nanostructured lipid carriers employing quality by design (QbD) as a tool: characterizations, permeability, and bioavailability studies.Drug delivery and translational research · 2022Article
- Risk assessment and molecular mechanism study of drug-drug interactions between rivaroxaban and tyrosine kinase inhibitors mediated by CYP2J2/3A4 and BCRP/P-gp.Frontiers in pharmacology · 2022Article
- Physiologically-Based Pharmacokinetic Modeling to Support the Clinical Management of Drug-Drug Interactions With Bictegravir.Clinical pharmacology and therapeutics · 2021Article
- Antiviral Drug Delivery System for Enhanced Bioactivity, Better Metabolism and Pharmacokinetic Characteristics.International journal of nanomedicine · 2021Review
- Physiologically-Based Pharmacokinetic Modeling to Predict the Clinical Efficacy of the Coadministration of Lopinavir and Ritonavir against SARS-CoV-2.Clinical pharmacology and therapeutics · 2020Article
- CYP2J2 Molecular Recognition: A New Axis for Therapeutic Design.Pharmacology & therapeutics · 2020Review
- Role of Arginine 117 in Substrate Recognition by Human Cytochrome P450 2J2.International journal of molecular sciences · 2018Article
- Cross-talk of cannabinoid and endocannabinoid metabolism is mediated via human cardiac CYP2J2.Journal of inorganic biochemistry · 2018Article
- Regulation of CYP2J2 and EET Levels in Cardiac Disease and Diabetes.International journal of molecular sciences · 2018Review
- Antiretroviral Drug Metabolism in Humanized PXR-CAR-CYP3A-NOG Mice.The Journal of pharmacology and experimental therapeutics · 2018Article
- Arachidonic Acid Metabolism by Human Cardiovascular CYP2J2 Is Modulated by Doxorubicin.Biochemistry · 2017Article
- Characterization of Atomoxetine Biotransformation and Implications for Development of PBPK Models for Dose Individualization in Children.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Ritonavir, an HIV protease inhibitor, is successfully used for the prevention and treatment of HIV infections. Ritonavir pharmacokinetics are complicated by inhibition, induction and pharmacogenetics of cytochrome P450 (CYP) enzymes mediating its clearance. This investigation revealed that CYP2J2, along with CYP3A4/5 and CYP2D6, efficiently metabolizes ritonavir, and to a CYP2J2-specific (minor) metabolite. Chemical inhibition of ritonavir metabolism, clearance, KI/kinact and abundance of CYP2J2 in liver microsomes were evaluated and then applied to an in vitro-in vivo static scaling model to estimate the contribution of each isozyme, as a function of CYP abundance, activity, and genotype. Disposition of the CYP2J2-specific metabolite was also evaluated in vivo. In plasma, metabolite abundance was well above previously reported levels with circulating concentrations measured at 2 μM for the main hydroxylisopropyl metabolite. Ritonavir and metabolite plasma profiles were simulated using Simcyp(®). A modest (2-6%) contribution of CYP2J2 to ritonavir clearance is predicted which increases to more than 20% in subjects carrying CYP2D6 poor metabolizer polymorphisms and CYP3A4 irreversible inhibition. These results indicate that minor drug metabolizing enzymes could become quantitatively important in RTV clearance if main metabolic pathways are impeded.
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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.