ArticleJournal of cystic fibrosis : official journal of the European Cystic Fibrosis Society2020
Accumulation and persistence of ivacaftor in airway epithelia with prolonged treatment.
Article in Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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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.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Triple potentiator combinations increase the functional correction of several CFTR gating mutants.npj drug discovery · 2026Article
- Targeting the Aryl Hydrocarbon Receptor: The Potential of Indole Compounds in the Treatment of Cystic Fibrosis.International journal of molecular sciences · 2025Review
- Article
- Therapeutic Drug Monitoring of Elexacaftor, Tezacaftor, and Ivacaftor in Adult People with Cystic Fibrosis.Journal of personalized medicine · 2024Article
- Differential distribution of ivacaftor and its metabolites in plasma and human airway epithelia.Pulmonary pharmacology & therapeutics · 2024Article
- Article
- Simultaneous Quantification of Ivacaftor, Tezacaftor, and Elexacaftor in Cystic Fibrosis Patients' Plasma by a Novel LC-MS/MS Method.Biomedicines · 2023Article
- Therapeutic Drug Monitoring of Ivacaftor, Lumacaftor, Tezacaftor, and Elexacaftor in Cystic Fibrosis: Where Are We Now?Pharmaceutics · 2022Review
- Net benefit of ivacaftor during prolonged tezacaftor/elexacaftor exposure in vitro.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2022Article
- Established and novel human translational models to advance cystic fibrosis research, drug discovery, and optimize CFTR-targeting therapeutics.Current opinion in pharmacology · 2022Review
- CFTR function and clinical response to modulators parallel nasal epithelial organoid swelling.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- CFTR Modulators: Does One Dose Fit All?Journal of personalized medicine · 2021Review
- Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCurrent dosing strategies of CFTR modulators are based on serum pharmacokinetics, but drug concentrations in target tissues such as airway epithelia are not known. Previous data suggest that CFTR modulators may accumulate in airway epithelia, and serum pharmacokinetics may not accurately predict effects of chronic treatment.
methodsCF (F508del homozygous) primary human bronchial epithelial (HBE) cells grown at air-liquid interface were treated for 14 days with ivacaftor plus lumacaftor or ivacaftor plus tezacaftor, followed by a 14-day washout period. At various intervals during treatment and washout phases, drug concentrations were measured via mass spectrometry, electrophysiological function was assessed in Ussing chambers, and mature CFTR protein was quantified by Western blotting.
resultsDuring treatment, ivacaftor accumulated in CF-HBEs to a much greater extent than either lumacaftor or tezacaftor and remained persistently elevated even after 14 days of washout. CFTR activity peaked at 7 days of treatment but diminished with further ivacaftor accumulation, though remained above baseline even after washout.
conclusionsIntracellular accrual and persistence of CFTR modulators during and after chronic treatment suggest complex pharmacokinetic and pharmacodynamic properties within airway epithelia that are not predicted by serum pharmacokinetics. Direct measurement of drugs in target tissues may be needed to optimize dosing strategies, and the persistence of CFTR modulators after treatment cessation has implications for personalized medicine approaches.
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Registered trials
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