ArticleThe AAPS journal2019
Simulating the Impact of Elevated Levels of Interleukin-6 on the Pharmacokinetics of Various CYP450 Substrates in Patients with Neuromyelitis Optica or Neuromyelitis Optica Spectrum Disorders in Different Ethnic Populations.
Article in The AAPS journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
17 citing papers in PubMed, 2 syntheses or guidelines pooled it, 25 citations in OpenAlex.
- The Cytokine Release Syndrome and/or the Proinflammatory Cytokines as Underlying Mechanisms of Downregulation of Drug Metabolism and Drug Transport: A Systematic Review of the Clinical Pharmacokinetics of Victim Drugs of this Drug-Disease Interaction Under Different Clinical Conditions.Clinical pharmacokinetics · 2022Pooled it
- A systematic review on disease-drug-drug interactions with immunomodulating drugs: A critical appraisal of risk assessment and drug labelling.British journal of clinical pharmacology · 2022Pooled it
- Trial
- Drug-Drug Interaction Risk Assessment Strategies for Biologics in Inflammatory Bowel Disease: A Literature-Based Evidence Mini-Review.Clinical and translational science · 2026Review
- Mechanistic Insights into Cytokine Antagonist-Drug Interactions: A Physiologically Based Pharmacokinetic Modelling Approach with Tocilizumab as a Case Study.Pharmaceutics · 2025Article
- Advancing rare disease therapeutics through digital twins: Opportunities in drug development and precision dosing.Computational and structural biotechnology journal · 2025Review
- Evaluating drug interaction potential from cytokine release syndrome using a physiologically based pharmacokinetic model: A case study of teclistamab.CPT: pharmacometrics & systems pharmacology · 2024Article
- Inflammation altered correlation between CYP2C19 genotype and CYP2C19 activity in patients receiving voriconazole.Clinical and translational science · 2024Article
- Evaluation of the potential impact on pharmacokinetics of various cytochrome P450 substrates of increasing IL-6 levels following administration of the T-cell bispecific engager glofitamab.CPT: pharmacometrics & systems pharmacology · 2024Article
- Assessment of CYP3A-mediated drug interaction via cytokine (IL-6) elevation for mosunetuzumab using physiologically-based pharmacokinetic modeling.CPT: pharmacometrics & systems pharmacology · 2024Article
- Assessment of the drug-drug interaction potential for therapeutic proteins with pro-inflammatory activities.Clinical and translational science · 2023Review
- Physiologically Based Pharmacokinetic Modelling to Investigate the Impact of the Cytokine Storm on CYP3A Drug Pharmacokinetics in COVID-19 Patients.Clinical pharmacology and therapeutics · 2022Article
- Physiologically based pharmacokinetic (PBPK) modeling of the role of CYP2D6 polymorphism for metabolic phenotyping with dextromethorphan.Frontiers in pharmacology · 2022Article
- Prediction of cytochromes P450 3A and 2C19 modulation by both inflammation and drug interactions using physiologically based pharmacokinetics.CPT: pharmacometrics & systems pharmacology · 2022Article
- Clinically Significant Drug Interactions Between Psychotropic Agents and Repurposed COVID-19 Therapies.CNS drugs · 2021Review
- Modeling Approach to Predict the Impact of Inflammation on the Pharmacokinetics of CYP2C19 and CYP3A4 Substrates.Pharmaceutical research · 2021Article
- Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature.Frontiers in pharmacology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A physiologically based pharmacokinetic (PBPK) model was used to simulate the impact of elevated levels of interleukin (IL)-6 on the exposure of several orally administered cytochrome P450 (CYP) probe substrates (caffeine, S-warfarin, omeprazole, dextromethorphan, midazolam, and simvastatin). The changes in exposure of these substrates in subjects with rheumatoid arthritis (and hence elevated IL-6 levels) compared with healthy subjects were predicted with a reasonable degree of accuracy. The PBPK model was then used to simulate the change in oral exposure of the probe substrates in North European Caucasian, Chinese, and Japanese population of patients with neuromyelitis optica (NMO) or NMO spectrum disorder with elevated plasma IL-6 levels (up to 100 pg/mL). Moderate interactions [mean AUC fold change, ≤ 2.08 (midazolam) or 2.36 (simvastatin)] was predicted for CYP3A4 probe substrates and weak interactions (mean AUC fold change, ≤ 1.29-1.97) were predicted for CYP2C19, CYP2C9, and CYP2D6 substrates. No notable interaction was predicted with CYP1A2. Although ethnic differences led to differences in simulated exposure for some of the probe substrates, there were no marked differences in the predicted magnitude of the change in exposure following IL-6-mediated suppression of CYPs. Decreased levels of serum albumin (as reported in NMO patients) had little impact on the magnitude of the simulated IL-6-mediated drug interactions. This PBPK modeling approach allowed us to leverage knowledge from different disease and ethnic populations to make predictions of cytokine-related DDIs in a rare disease population where actual clinical studies would otherwise be difficult to conduct.
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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.