ArticleCancer chemotherapy and pharmacology2020
Physiologically based pharmacokinetic modeling to assess metabolic drug-drug interaction risks and inform the drug label for fedratinib.
Article in Cancer chemotherapy and pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Pharmacokinetics, distribution, metabolism, excretion and safety characterization of ZJCK-6-72: novel DYRK1A inhibitor with optimized brain exposure for Alzheimer's disease therapy.Frontiers in pharmacology · 2026Article
- 1β-Hydroxydeoxycholic acid as an endogenous biomarker in human plasma for assessment of drug-drug interaction with moderate CYP3A inhibitor.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Advancements in physiologically based pharmacokinetic modeling for fedratinib: updating dose guidance in the presence of a dual inhibitor of CYP3A4 and CYP2C19.Cancer chemotherapy and pharmacology · 2024Article
- Preclinical Systemic Pharmacokinetics, Dose Proportionality, and Central Nervous System Distribution of the ATM Inhibitor WSD0628, a Novel Radiosensitizer for the Treatment of Brain Tumors.The Journal of pharmacology and experimental therapeutics · 2024Article
- Application of physiologically based pharmacokinetics modeling in the research of small-molecule targeted anti-cancer drugs.Cancer chemotherapy and pharmacology · 2023Review
- Pharmacokinetic and Pharmacodynamic Drug-Drug Interactions: Research Methods and Applications.Metabolites · 2023Review
- In-Depth Analysis of Physiologically Based Pharmacokinetic (PBPK) Modeling Utilization in Different Application Fields Using Text Mining Tools.Pharmaceutics · 2022Review
- Involvement of Transporters in Intestinal Drug-Drug Interactions of Oral Targeted Anticancer Drugs Assessed by Changes in Drug Absorption Time.Pharmaceutics · 2022Article
- Effect of fluconazole on the pharmacokinetics of a single dose of fedratinib in healthy adults.Cancer chemotherapy and pharmacology · 2022Article
- Prediction of drug-drug interaction potential mediated by transporters between dasatinib and metformin, pravastatin, and rosuvastatin using physiologically based pharmacokinetic modeling.Cancer chemotherapy and pharmacology · 2022Article
- Impact of fedratinib on the pharmacokinetics of transporter probe substrates using a cocktail approach.Cancer chemotherapy and pharmacology · 2021Article
- Effects of strong and moderate CYP3A4 inducers on the pharmacokinetics of fedratinib in healthy adult participants.Cancer chemotherapy and pharmacology · 2021Article
- Application of Physiologically Based Pharmacokinetic Modeling to Evaluate the Drug-Drug and Drug-Disease Interactions of Apatinib.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeFedratinib (INREBIC
methodsThe physiologically based pharmacokinetic (PBPK) model of fedratinib was constructed in Simcyp
resultsThe validated PBPK model was applied to predict DDIs between fedratinib and CYP modulators or substrates. The model simulations indicated that the fedratinib-as-victim DDI extent in terms of geometric mean area under curve (AUC) at steady state is about twofold or 1.2-fold when strong or moderate CYP3A4 inhibitors, respectively, are co-administered with repeated doses of fedratinib. In addition, the PBPK model successfully captured the perpetrator DDI effect of fedratinib on a sensitive CY3A4 substrate midazolam and predicted minor effects of fedratinib on CYP2C8/9 substrates.
conclusionsThe PBPK-DDI model of fedratinib facilitated drug development by identifying DDI potential, optimizing clinical study designs, supporting waivers for clinical studies, and informing drug label claims. Fedratinib dose should be reduced to 200 mg QD when a strong CYP3A4 inhibitor is co-administered and then re-escalated to 400 mg in a stepwise manner as tolerated after the strong CYP3A4 inhibitor is discontinued.
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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.