ArticleClinical pharmacokinetics2025
Static Versus Dynamic Model Predictions of Competitive Inhibitory Metabolic Drug-Drug Interactions via Cytochromes P450: One Step Forward and Two Steps Backwards.
Article in Clinical pharmacokinetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
7 citing papers in PubMed.
- Integrating Static and Dynamic Models to Predict Cannabidiol-Mediated Metabolic Drug-Drug Interactions.Clinical pharmacology and therapeutics · 2026Article
- Development of an Empirical Approach for the Prediction of Cytochrome P450-Based Drug-Drug Interactions in Pediatric Patients.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Addressing a Common Misconception of Simple Additive and Cumulative Drug Inhibition: Multiple Weak Inhibitors of Common Metabolic Pathway Do Not Pose a Strong Interaction Risk!Journal of clinical pharmacology · 2026Article
- Pharmacokinetics and Drug Interactions.Pharmaceutics · 2026Article
- Development and functional characterization of a tissue-engineered blood-air barrier model forNanomedicine (London, England) · 2025Article
- Caution with PBPK Modeling Based on the In Vitro Kinetics for Bilirubin Hepatic Uptake and Glucuronidation: Commentary on Dong et al.Clinical pharmacology and therapeutics · 2025Article
- A Review on New Frontiers in Drug-Drug Interaction Predictions and Safety Evaluations with In Vitro Cellular Models.Pharmaceutics · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPredicting metabolic drug-drug interactions (DDIs) via cytochrome P450 enzymes (CYP) is essential in drug development, but controversy has reemerged recently about whether in vitro-in vivo extrapolation (IVIVE) using static models can replace dynamic models for some regulatory filings and label recommendations.
objectiveThe aim of this study was to determine if static and dynamic models are equivalent for the quantitative prediction of metabolic DDIs arising from competitive CYP inhibition.
methodsDrug parameter spaces were varied to simulate 30,000 DDIs between hypothetical substrates and inhibitors of CYP3A4. Predicted area under the plasma concentration-time profile ratios for substrates (AUCr = AUC
resultsThe highest rate of IMDR <0.8 and IMDR >1.25 discrepancies in the 'population' representative was 85.9% and 3.1%, respectively, when using C
conclusionStatic models are not equivalent to dynamic models for predicting metabolic DDIs via competitive CYP inhibition across diverse drug parameter spaces, particularly for vulnerable patients. Caution is warranted in drug development if static IVIVE approaches are used alone to evaluate metabolic DDI risks.
Indexed as
Identifiers
What OpenQuestion holds
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.