ArticleChemical research in toxicology2011
Metabolomic screening and identification of the bioactivation pathways of ritonavir.
Article in Chemical research in toxicology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Potential pharmacokinetic interactions with concurrent use of herbal medicines and a ritonavir-boosted COVID-19 protease inhibitor in low and middle-income countries.Frontiers in pharmacology · 2023Review
- The Mechanism-Based Inactivation of CYP3A4 by Ritonavir: What Mechanism?International journal of molecular sciences · 2022Review
- Long Noncoding RNAs Hepatocyte Nuclear Factor 4A Antisense RNA 1 and Hepatocyte Nuclear Factor 1A Antisense RNA 1 Are Involved in Ritonavir-Induced Cytotoxicity in Hepatoma Cells.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- Metabolism of a Selective Serotonin and Norepinephrine Reuptake Inhibitor Duloxetine in Liver Microsomes and Mice.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- In Vitro Metabolism of Donepezil in Liver Microsomes Using Non-Targeted Metabolomics.Pharmaceutics · 2021Article
- Metabolic profiling of norepinephrine reuptake inhibitor atomoxetine.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2020Article
- Metabolism of JQ1, an inhibitor of bromodomain and extra terminal bromodomain proteins, in human and mouse liver microsomes†.Biology of reproduction · 2020Article
- Pregnane X receptor activation potentiates ritonavir hepatotoxicity.The Journal of clinical investigation · 2019Article
- Identification of Novel Pathways in Idelalisib Metabolism and Bioactivation.Chemical research in toxicology · 2018Article
- Antiretroviral Drug Metabolism in Humanized PXR-CAR-CYP3A-NOG Mice.The Journal of pharmacology and experimental therapeutics · 2018Article
- Inhibition of Human CYP3A4 by Rationally Designed Ritonavir-Like Compounds: Impact and Interplay of the Side Group Functionalities.Molecular pharmaceutics · 2018Article
- Revisiting the Metabolism and Bioactivation of Ketoconazole in Human and Mouse Using Liquid Chromatography-Mass Spectrometry-Based Metabolomics.International journal of molecular sciences · 2017Article
- The Opportunities of Metabolomics in Drug Safety Evaluation.Current pharmacology reports · 2017Article
- Biotransformation of Cobicistat: Metabolic Pathways and Enzymes.Drug metabolism letters · 2016Article
- Transgenic mice and metabolomics for study of hepatic xenobiotic metabolism and toxicity.Expert opinion on drug metabolism & toxicology · 2015Review
- Subpopulations of myeloid-derived suppressor cells impair T cell responses through independent nitric oxide-related pathways.International journal of cancer · 2014Article
- CPY3A4-mediated α-hydroxyaldehyde formation in saquinavir metabolism.Drug metabolism and disposition: the biological fate of chemicals · 2014Article
- The effect of ritonavir on human CYP2B6 catalytic activity: heme modification contributes to the mechanism-based inactivation of CYP2B6 and CYP3A4 by ritonavir.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- Pyridine-substituted desoxyritonavir is a more potent inhibitor of cytochrome P450 3A4 than ritonavir.Journal of medicinal chemistry · 2013Article
- Towards polypharmacokinetics: pharmacokinetics of multicomponent drugs and herbal medicines using a metabolomics approach.Evidence-based complementary and alternative medicine : eCAM · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Ritonavir-boosted protease inhibitor regimens are widely used for HIV chemotherapy. However, ritonavir causes multiple side effects, and the mechanisms are not fully understood. The current study was designed to explore the metabolic pathways of ritonavir that may be related to its toxicity. Metabolomic analysis screened out 26 ritonavir metabolites in mice, and half of them are novel. These novel ritonavir metabolites include two glycine conjugated, two N-acetylcysteine conjugated, and three ring-open products. Accompanied with the generation of ritonavir ring-open metabolites, the formation of methanethioamide and 2-methylpropanethioamide were expected. Upon the basis of the structures of these novel metabolites, five bioactivation pathways are proposed, which may be associated with sulfation and epoxidation. By using Cyp3a-null mice, we confirmed that CYP3A is involved in four pathways of RTV bioactivation. In addition, all these five bioactivation pathways were recapitulated in the incubation of ritonavir in human liver microsomes. Further studies are suggested to determine the role of CYP3A and these bioactivation pathways in ritonavir toxicity.
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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.