ArticleDrug metabolism letters2018
Cytochrome P450 3A4 Induction: Lumacaftor versus Ivacaftor Potentially Resulting in Significantly Reduced Plasma Concentration of Ivacaftor.
Article in Drug metabolism letters, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Assessing the Labeling Information on Drugs Associated With Suicide Risk: Systematic Review.JMIR public health and surveillance · 2024Pooled it
- Predictive capacity of paediatric nasal epithelial cells in sequential CFTR modulator therapy.Thorax · 2026Article
- Article
- A Liquid Chromatography-Tandem Mass Spectrometry Method for the Quantification of Cystic Fibrosis Drugs (Caftors) in Plasma and Its Application for Therapeutic Monitoring.Molecules (Basel, Switzerland) · 2025Article
- Cystic Fibrosis Treatment Landscape: Progress, Challenges, and Future Directions.Turkish archives of pediatrics · 2025Article
- Differential distribution of ivacaftor and its metabolites in plasma and human airway epithelia.Pulmonary pharmacology & therapeutics · 2024Article
- Hydrocodone, Oxycodone, and Morphine Metabolism and Drug-Drug Interactions.The Journal of pharmacology and experimental therapeutics · 2023Review
- Ocular development after highly effective modulator treatment early in life.Frontiers in pharmacology · 2023Review
- Ivacaftor Alters Macrophage and Lymphocyte Infiltration in the Lungs Following Lipopolysaccharide Exposure.ACS pharmacology & translational science · 2022Article
- The L467F-F508del Complex Allele Hampers Pharmacological Rescue of Mutant CFTR by Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis Patients: The Value of the Ex Vivo Nasal Epithelial Model to Address Non-Responders to CFTR-Modulating Drugs.International journal of molecular sciences · 2022Article
- An evaluation of ledipasvir + sofosbuvir for the treatment of chronic hepatitis C infection.Expert opinion on pharmacotherapy · 2021Review
- State of the Art on Approved Cystic Fibrosis Transmembrane Conductance Regulator (Pharmaceuticals (Basel, Switzerland) · 2021Review
- The Intestinal Microbiome and Cystic Fibrosis Transmembrane Conductance Regulator Modulators: Emerging Themes in the Management of Gastrointestinal Manifestations of Cystic Fibrosis.Current gastroenterology reports · 2021Review
- Anti-Inflammatory Influences of Cystic Fibrosis Transmembrane Conductance Regulator Drugs on Lung Inflammation in Cystic Fibrosis.International journal of molecular sciences · 2021Review
- A Precision Medicine Approach to Optimize Modulator Therapy for Rare CFTR Folding Mutants.Journal of personalized medicine · 2021Article
- New Therapies to Correct the Cystic Fibrosis Basic Defect.International journal of molecular sciences · 2021Review
- Insights Into Patient Variability During Ivacaftor-Lumacaftor Therapy in Cystic Fibrosis.Frontiers in pharmacology · 2021Article
- Treatment of Polarized Cystic Fibrosis Airway Cells With HGF Prevents VX-661-Rescued F508del-CFTR Destabilization Caused by Prolonged Co-exposure to VX-770.Frontiers in molecular biosciences · 2021Article
- The Balance between the Safety of Mother, Fetus, and Newborn Undergoing Cystic Fibrosis Transmembrane Conductance Regulator Treatments during Pregnancy.ACS pharmacology & translational science · 2020Review
- Contraceptive use among women with cystic fibrosis: A pilot study linking reproductive health questions to the Cystic Fibrosis Foundation National Patient Registry.Contraception · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
objectiveSince the release of ivacaftor-lumacaftor, several red-flags have been raised that highlight the clinical efficacy of this combination strategy that may be limited due to antagonistic drug-drug interactions.
methodThe effect of ivacaftor, its major metabolites M1 and M6, lumacaftor and the novel cystic fibrosis transmembrane conductance regulator (CFTR) modulator tezacaftor at 10 µg/mL on the enzymatic activity of the major xenobiotic metabolizing enzymes CYP1A2 and CYP3A4 as well as the minor enzymes CYP2B6 and CYP2C9 was assayed.
resultsLumacaftor (3.74 x 105 ± 3.11 x 104 RLU), and ivacaftor-M6 (3.43 x 105 ± 7.61 x 103 RLU) markedly induced the activity of CYP3A4. Ivacaftor (2.22 x 105 ± 3.94 x 104 RLU) showed a lower relative ratio of luminescence units compared to chloramphenicol (3.17 x 105 ± 1.55 x 104 RLU). Interestingly, ivacaftor-M1 (6.74 x 104 ± 3.09 x 104 RLU) and the novel CFTR modulator tezacaftor (2.40 x 104 ± 8.14 x 104 RLU) did not show CYP3A4 induction. In the CYP1A2 and CYP2C9 assay, all metabolites showed a decrease in the ratio of luminescence units compared to the controls. Ivacaftor, its major metabolites, lumacaftor and tezacaftor all showed a slight increase in the ratio of luminescence units compared to the control rifampin with CYP2B6.
conclusionAll in all, present findings would suggest that lumacaftor and ivacaftor-M6 are strong inducers of CYP3A4, potentially reducing ivacaftor concentrations; ivacaftor itself induces CYP3A4 to some extent.
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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.