ArticleCPT: pharmacometrics & systems pharmacology2022
Prediction of CYP-mediated DDIs involving inhibition: Approaches to address the requirements for system qualification of the Simcyp Simulator.
Article in CPT: pharmacometrics & systems pharmacology, 2022. 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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Who cites it
18 citing papers in PubMed, 39 citations in OpenAlex.
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- Development of an isavuconazole physiologically-based pharmacokinetic model for adult and pediatric populations.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Straight to Phase III: Model-Informed Approach Speeds Depemokimab Clinical Development in Interleukin-5-Driven Diseases.Clinical pharmacology and therapeutics · 2026Article
- Exploring the roles of cytochrome P450 enzymes and their inhibitors in cancers and non-neoplastic human diseases.Archives of pharmacal research · 2025Review
- Application of Physiologically-Based Pharmacokinetic Modeling to Support Drug Labeling: Prediction of CYP3A4-Mediated Pirtobrutinib-Drug Interactions.CPT: pharmacometrics & systems pharmacology · 2025Article
- Physiologically Based Pharmacokinetic (PBPK) Model to Predict the Magnitude of Drug-Drug Interaction Between Fezolinetant and CYP1A2 Inhibitors.Journal of clinical pharmacology · 2025Article
- Mechanistic Insights into Cytokine Antagonist-Drug Interactions: A Physiologically Based Pharmacokinetic Modelling Approach with Tocilizumab as a Case Study.Pharmaceutics · 2025Article
- Variability in intestinal drug metabolizing enzymes and transporters in Crohn's disease and potential impact on oral drug absorption.British journal of clinical pharmacology · 2025Article
- Static Versus Dynamic Model Predictions of Competitive Inhibitory Metabolic Drug-Drug Interactions via Cytochromes P450: One Step Forward and Two Steps Backwards.Clinical pharmacokinetics · 2025Article
- Ameliorative Effects of Ethyl-Acetate Extract ofF1000Research · 2025Article
- Establishing a physiologically based pharmacokinetic framework for aldehyde oxidase and dual aldehyde oxidase-CYP substrates.CPT: pharmacometrics & systems pharmacology · 2025Article
- Evaluating drug interaction potential from cytokine release syndrome using a physiologically based pharmacokinetic model: A case study of teclistamab.CPT: pharmacometrics & systems pharmacology · 2024Article
- Applied physiologically-based pharmacokinetic modeling to assess uridine diphosphate-glucuronosyltransferase-mediated drug-drug interactions for Vericiguat.CPT: pharmacometrics & systems pharmacology · 2024Article
- A comprehensive evaluation in clinic and physiologically-based pharmacokinetic modeling and simulation to confirm lack of cytochrome P450-mediated drug-drug interaction potential for pomotrelvir.CPT: pharmacometrics & systems pharmacology · 2023Article
- Development and application of a PBPK modeling strategy to support antimalarial drug development.CPT: pharmacometrics & systems pharmacology · 2023Article
- Tiered approach to evaluate the CYP3A victim and perpetrator drug-drug interaction potential for vonoprazan using PBPK modeling and clinical data to inform labeling.CPT: pharmacometrics & systems pharmacology · 2023Article
- Comparing the applications of machine learning, PBPK, and population pharmacokinetic models in pharmacokinetic drug-drug interaction prediction.CPT: pharmacometrics & systems pharmacology · 2022Review
- Prediction of CYP-mediated DDIs involving inhibition: Approaches to address the requirements for system qualification of the Simcyp Simulator.CPT: pharmacometrics & systems pharmacology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Physiologically-based pharmacokinetic (PBPK) modeling is being increasingly used in drug development to avoid unnecessary clinical drug-drug interaction (DDI) studies and inform drug labels. Thus, regulatory agencies are recommending, or indeed requesting, more rigorous demonstration of the prediction accuracy of PBPK platforms in the area of their intended use. We describe a framework for qualification of the Simcyp Simulator with respect to competitive and mechanism-based inhibition (MBI) of CYP1A2, CYP2D6, CYP2C8, CYP2C9, CYP2C19, and CYP3A4/5. Initially, a DDI matrix, consisting of a range of weak, moderate, and strong inhibitors and substrates with varying fraction metabolized by specific CYP enzymes that were susceptible to different degrees of inhibition, were identified. Simulations were run with 123 clinical DDI studies involving competitive inhibition and 78 clinical DDI studies involving MBI. For competitive inhibition, the overall prediction accuracy was good with an average fold error (AFE) of 0.91 and 0.92 for changes in the maximum plasma concentration (C
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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.