Evidence map›Paper›PMID 40405059›Full record

Observational studyClinical pharmacokinetics2025

Population Pharmacokinetics of Elexacaftor, Tezacaftor and Ivacaftor in a Real-World Cohort of Adults with Cystic Fibrosis.

Paulette Magnas, Naïm Bouazza, Frantz Foissac, Léo Froelicher Bournaud, Gabrielle Lui, Nicolas Carlier, Jennifer Da Silva, Johanna Fesenbeckh, Reem Kanaan, Isabelle Honoré and 4 more

Abstract readObservational Study
PubMed Publisher
In one paragraph

Observational study in Clinical pharmacokinetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Observational
  3. Article
  4. Observational
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Paulette MagnasU1343, Pharmacologie et évaluations thérapeutiques chez l'enfant et la femme enceinte, Inserm, Université Paris Cité, Paris, France. paulette.magnas@aphp.fr.
Naïm BouazzaU1343, Pharmacologie et évaluations thérapeutiques chez l'enfant et la femme enceinte, Inserm, Université Paris Cité, Paris, France.
Frantz FoissacU1343, Pharmacologie et évaluations thérapeutiques chez l'enfant et la femme enceinte, Inserm, Université Paris Cité, Paris, France.
Léo Froelicher BournaudU1343, Pharmacologie et évaluations thérapeutiques chez l'enfant et la femme enceinte, Inserm, Université Paris Cité, Paris, France.
Gabrielle LuiU1343, Pharmacologie et évaluations thérapeutiques chez l'enfant et la femme enceinte, Inserm, Université Paris Cité, Paris, France.
Nicolas CarlierService de Pneumologie, Centre National de Référence de la Mucoviscidose, Hôpital Cochin, AP-HP, Paris, France.
Jennifer Da SilvaService de Pneumologie, Centre National de Référence de la Mucoviscidose, Hôpital Cochin, AP-HP, Paris, France.
Johanna FesenbeckhService de Pneumologie, Centre National de Référence de la Mucoviscidose, Hôpital Cochin, AP-HP, Paris, France.
Reem KanaanService de Pneumologie, Centre National de Référence de la Mucoviscidose, Hôpital Cochin, AP-HP, Paris, France.
Isabelle HonoréService de Pneumologie, Centre National de Référence de la Mucoviscidose, Hôpital Cochin, AP-HP, Paris, France.
Clémence MartinService de Pneumologie, Centre National de Référence de la Mucoviscidose, Hôpital Cochin, AP-HP, Paris, France.
Jean-Marc TreluyerU1343, Pharmacologie et évaluations thérapeutiques chez l'enfant et la femme enceinte, Inserm, Université Paris Cité, Paris, France.
Pierre-Régis BurgelService de Pneumologie, Centre National de Référence de la Mucoviscidose, Hôpital Cochin, AP-HP, Paris, France.
Sihem BenaboudU1343, Pharmacologie et évaluations thérapeutiques chez l'enfant et la femme enceinte, Inserm, Université Paris Cité, Paris, France.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesElexacaftor-tezacaftor-ivacaftor (ETI), a combination of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, has become the therapeutic standard of care for most people with cystic fibrosis (pwCF). People with cystic fibrosis exhibit differences in CFTR genotypes and have important differences in phenotypic characteristics including age, body weight, pancreatic status, disease severity, and comorbidities. While these differences predict large interindividual variability (IIV) in ETI exposure, there is a unique dose regimen recommended for adults. This raises questions around the "one-dose fits all" strategy.

objectivesThe aims of this study were to describe real-world population pharmacokinetics (Pop-PK) of ETI in adults with CF and identify factors associated with IIV.

methodAs part of the ongoing French national observational cohort study the Pop-PK analysis included 552 plasma concentrations drawn routinely from 325 adults with CF.

resultsA one-compartment model with first order absorption and elimination best represented all three compounds, and an additional lag-time for elexacaftor PK data. Large IIV was observed in ETI, with an area under the curve (AUC

conclusionThis study established the first ETI Pop-PK analysis in adults with CF and identified several covariates that explain IIV. Therapeutic drug monitoring may be beneficial for patients with a small body weight, older ages, carrying one ETI-responsive CFTR variant or those with no exocrine pancreatic insufficiency and especially for patients who combine these characteristics. Therapeutic drug monitoring may also prove to be useful in individuals experiencing adverse events, in those with reduced effectiveness, or to help manage non-adherence issues.

Indexed as

AminophenolsBenzodioxolesCystic FibrosisIndolesPyrazolesPyridinesPyrrolidinesQuinolonesAdolescentAdultChloride Channel AgonistsCohort StudiesCystic Fibrosis Transmembrane Conductance RegulatorDrug CombinationsFemaleHumansAminophenolsBenzodioxolesCFTR protein, humanChloride Channel AgonistsCystic Fibrosis Transmembrane Conductance RegulatorDrug Combinationselexacaftorelexacaftor, ivacaftor, tezacaftor drug combinationIndolesivacaftorPyrazolesPyridinesPyrrolidinesQuinolinesQuinolonestezacaftortezacaftor, ivacaftor drug combination

Identifiers

PMID40405059

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

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.