ArticleMolecular pharmaceutics2018
Improved Predictions of Drug-Drug Interactions Mediated by Time-Dependent Inhibition of CYP3A.
Article in Molecular pharmaceutics, 2018. 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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Who cites it
21 citing papers in PubMed.
- A Physiologically Based Pharmacokinetic Model to Predict Potential Drug-Drug Interactions of TPN171, a Novel Phosphodiesterase Type 5 Inhibitor.CPT: pharmacometrics & systems pharmacology · 2026Article
- Enzyme-substrate-inactivator complex formation can impact time-dependent inhibition kinetics.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Application of Physiologically-Based Pharmacokinetic Modeling to Support Drug Labeling: Prediction of CYP3A4-Mediated Pirtobrutinib-Drug Interactions.CPT: pharmacometrics & systems pharmacology · 2025Article
- 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
- Influence of a Short Course of Ritonavir Used as Booster in Antiviral Therapies Against SARS-CoV-2 on the Exposure of Atorvastatin and Rosuvastatin.Cardiovascular drugs and therapy · 2025Article
- A preliminary exploration of liver microsomes and PBPK to uncover the impact of CYP3A4/5 and CYP2C19 on tacrolimus and voriconazole drug-drug interactions.Scientific reports · 2025Article
- Development of a PBPK model to quantitatively understand absorption and disposition mechanism and support future clinical trials for PB-201.CPT: pharmacometrics & systems pharmacology · 2023Article
- The inhibitory and inducing effects of ritonavir on hepatic and intestinal CYP3A and other drug-handling proteins.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Review
- The Mechanism-Based Inactivation of CYP3A4 by Ritonavir: What Mechanism?International journal of molecular sciences · 2022Review
- 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
- Prediction of pyrotinib exposure based on physiologically-based pharmacokinetic model and endogenous biomarker.Frontiers in pharmacology · 2022Article
- 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
- 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
- Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations.The Journal of pharmacology and experimental therapeutics · 2021Article
- Prediction of Drug Clearance from Enzyme and Transporter Kinetics.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Irreversible Enzyme Inhibition Kinetics and Drug-Drug Interactions.Methods in molecular biology (Clifton, N.J.) · 2021Article
- 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
- Time-dependent enzyme inactivation: Numerical analyses of in vitro data and prediction of drug-drug interactions.Pharmacology & therapeutics · 2020Review
- Numerical Analysis of Time-Dependent Inhibition by MDMA.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Time-dependent inactivation (TDI) of cytochrome P450s (CYPs) is a leading cause of clinical drug-drug interactions (DDIs). Current methods tend to overpredict DDIs. In this study, a numerical approach was used to model complex CYP3A TDI in human-liver microsomes. The inhibitors evaluated included troleandomycin (TAO), erythromycin (ERY), verapamil (VER), and diltiazem (DTZ) along with the primary metabolites N-demethyl erythromycin (NDE), norverapamil (NV), and N-desmethyl diltiazem (NDD). The complexities incorporated into the models included multiple-binding kinetics, quasi-irreversible inactivation, sequential metabolism, inhibitor depletion, and membrane partitioning. The resulting inactivation parameters were incorporated into static in vitro-in vivo correlation (IVIVC) models to predict clinical DDIs. For 77 clinically observed DDIs, with a hepatic-CYP3A-synthesis-rate constant of 0.000 146 min
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