ArticleFrontiers in pharmacology2022
The Influence of CYP3A4 Genetic Polymorphism and Proton Pump Inhibitors on Osimertinib Metabolism.
Article in Frontiers in pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- Physiologically Based Pharmacokinetic Modeling to Assess Antiretroviral-BTK Inhibitor Interactions and Provide Recommendations for Co-Administration Regimens.Pharmaceutics · 2026Article
- Treatment adherence and clinical outcomes of osimertinib in minority patients with advanced EGFR mutated NSCLC.NPJ precision oncology · 2026Article
- Pharmacodynamics, pharmacokinetics, interactions with other drugs, toxicity and clinical effectiveness of proton pump inhibitors.Frontiers in pharmacology · 2025Review
- The influence of drug-induced metabolic enzyme activity inhibition and CYP3A4 gene polymorphism on aumolertinib metabolism.Frontiers in pharmacology · 2024Article
- Exploring inter-ethnic and inter-patient variability and optimal dosing of osimertinib: a physiologically based pharmacokinetic modeling approach.Frontiers in pharmacology · 2024Article
- Review
- Effects of CYP3A4/5 and ABC transporter polymorphisms on osimertinib plasma concentrations in Japanese patients with non-small cell lung cancer.Investigational new drugs · 2022Article
- Combination Use of First-Line Afatinib and Proton-Pump Inhibitors Reduces Overall Survival Among Patients with EGFFR Mutant Lung Cancer.OncoTargets and therapy · 2022Article
- Use of modeling and simulation to predict the influence of triazole antifungal agents on the pharmacokinetics of zanubrutinib and acalabrutinib.Frontiers in pharmacology · 2022Article
- Instability Mechanism of Osimertinib in Plasma and a Solving Strategy in the Pharmacokinetics Study.Frontiers in pharmacology · 2022Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aim of this study was to 1) investigate the effects of 27 CYP3A4 variants on the metabolism of osimertinib and 2) study the interactions between osimertinib and others as well as the underlying mechanism. A recombinant human CYP3A4 enzymatic incubation system was developed and employed to determine the kinetic profile of CYP3A4 variants. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was applied to detect the concentration of the main metabolite, AZ5104. The results demonstrated that the relative clearance rates of CYP3A4.19, 10, 18, 5, 16, 14, 11, 2, 13, 12, 7, 8, and 17 in catalyzing osimertinib were significantly reduced to a minimum of 25.68% compared to CYP3A4.1, while those of CYP3A4.29, 32, 33, 28, 15, 34, and 3 were obviously enhanced, ranging from 114.14% to 284.52%. The activities of the remaining variants were almost equal to those of CYP3A4.1. In addition, 114 drugs were screened to determine the potential interaction with osimertinib based on the rat liver microsome (RLM) reaction system. Sixteen of them inhibited the production of AZ5104 to 20% or less, especially proton pump inhibitors, among which the IC
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