ReviewPharmacology & therapeutics2020
Time-dependent enzyme inactivation: Numerical analyses of in vitro data and prediction of drug-drug interactions.
Review in Pharmacology & therapeutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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.
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Who cites it
18 citing papers in PubMed.
- A real-time FRET ubiquitin transfer assay for quantitative characterization of ternary complexes in targeted protein degradation.Cell reports methods · 2026Article
- Kinetic Analysis of Irreversible Covalent Enzyme Inhibitors and Its Use in Drug Design.International journal of molecular sciences · 2026Review
- Enzyme-substrate-inactivator complex formation can impact time-dependent inhibition kinetics.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Phytomedicine-mediated time-dependent inactivation of CYP3A4 by chemical modification.Journal of pharmaceutical analysis · 2026Review
- Role of metabolites in drug-drug interactions.Drug metabolism and pharmacokinetics · 2026Review
- Modeling Metabolite Kinetics with a Partial Differential Equation-Based Hepatic Sinusoidal Model and MALDI-Mass Spectrometry Imaging of Verapamil and Its Metabolites.Journal of medicinal chemistry · 2026Article
- Optimization of In Vitro CYP3A4 TDI Assay Conditions and Use of Derived Parameters for Clinical DDI Risk Assessment Using Static and Dynamic Models.The AAPS journal · 2025Article
- Investigation ofPharmaceutics · 2023Article
- In-Silico Drug Toxicity and Interaction Prediction for Plant Complexes Based on Virtual Screening and Text Mining.International journal of molecular sciences · 2022Article
- Using partition analysis as a facile method to derive net clearances.Clinical and translational science · 2022Article
- Epigenetics in drug disposition & drug therapy: symposium report of the 24Drug metabolism reviews · 2022Review
- Complex Cytochrome P450 Kinetics Due to Multisubstrate Binding and Sequential Metabolism. Part 2. Modeling of Experimental Data.Drug metabolism and disposition: the biological fate of chemicals · 2021Article
- Complex Cytochrome P450 Kinetics Due to Multisubstrate Binding and Sequential Metabolism. Part 1. Theoretical Considerations.Drug metabolism and disposition: the biological fate of chemicals · 2021Article
- Irreversible Enzyme Inhibition Kinetics and Drug-Drug Interactions.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Numerical Methods for Modeling Enzyme Kinetics.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Multienzyme Kinetics and Sequential Metabolism.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Site-Directed Mutagenesis at the Molybdenum Pterin Cofactor Site of the Human Aldehyde Oxidase: Interrogating the Kinetic Differences Between Human and Cynomolgus Monkey.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Mechanisms of Herb-Drug Interactions Involving Cinnamon and CYP2A6: Focus on Time-Dependent Inhibition by Cinnamaldehyde and 2-Methoxycinnamaldehyde.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Cytochrome P450 (CYP) enzyme kinetics often do not conform to Michaelis-Menten assumptions, and time-dependent inactivation (TDI) of CYPs displays complexities such as multiple substrate binding, partial inactivation, quasi-irreversible inactivation, and sequential metabolism. Additionally, in vitro experimental issues such as lipid partitioning, enzyme concentrations, and inactivator depletion can further complicate the parameterization of in vitro TDI. The traditional replot method used to analyze in vitro TDI datasets is unable to handle complexities in CYP kinetics, and numerical approaches using ordinary differential equations of the kinetic schemes offer several advantages. Improvement in the parameterization of CYP in vitro kinetics has the potential to improve prediction of clinical drug-drug interactions (DDIs). This manuscript discusses various complexities in TDI kinetics of CYPs, and numerical approaches to model these complexities. The extrapolation of CYP in vitro TDI parameters to predict in vivo DDIs with static and dynamic modeling is discussed, along with a discussion on current gaps in knowledge and future directions to improve the prediction of DDI with in vitro data for CYP catalyzed drug metabolism.
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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.