Evidence map›Paper›PMID 42185741›Full record

Observational studyBritish journal of clinical pharmacology2026

Pregnancy-related effect on elexacaftor, tezacaftor and ivacaftor pharmacokinetics in women with cystic fibrosis.

Paulette Magnas, Naim Bouazza, Frantz Foissac, Saïk Urien, Léo Froelicher-Bournaud, Gabrielle Lui, Victoria Guillemart, Nicolas Carlier, Jennifer Da Silva, Johanna Fesenbeckh and 7 more

Abstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in British journal of clinical pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Observational
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

17 authors.

Paulette MagnasU1343, Pharmacologie et Évaluations Thérapeutiques Chez L'enfant et la Femme Enceinte, Inserm, Université Paris Cité, Paris, France.ORCID https://orcid.org/0009-0004-7201-3473
Naim BouazzaU1343, Pharmacologie et Évaluations Thérapeutiques Chez L'enfant et la Femme Enceinte, Inserm, Université Paris Cité, Paris, France.ORCID https://orcid.org/0000-0002-2158-1399
Frantz FoissacU1343, Pharmacologie et Évaluations Thérapeutiques Chez L'enfant et la Femme Enceinte, Inserm, Université Paris Cité, Paris, France.ORCID https://orcid.org/0000-0002-9928-3404
Saïk UrienUnité de Recherche Clinique, Université Paris Cité Necker/Cochin, Hôpital Tarnier, 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.
Victoria GuillemartCIC-1419, Inserm, Hôpitaux Cochin-Necker, 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.ORCID https://orcid.org/0000-0002-2045-4742
Vassilis TsatsarisUniversité Paris Cité, Maternité Port Royal, AP-HP, 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

Association Vaincre la Mucoviscidose, Filière Maladies Rares MUCO-CFTR, Société Française de la Mucoviscidose
6 · The paper itself

Abstract

aimThe number of pregnancies among women with cystic fibrosis (wwCF) has steadily increased over the past decade. However, the pharmacokinetics (PK) of elexacaftor-tezacaftor-ivacaftor (ETI) during gestation remains uncharacterized, despite its widespread use in this population. To date, no clinical trials have investigated the effectiveness, safety or PK profiles of ETI during pregnancy. Given the significant physiological changes that occur throughout gestation, which can alter drug PK, characterizing how pregnancy impacts ETI exposure represents a key step towards informing appropriate dosing strategies. Therefore, the aim of this analysis was to assess pregnancy effect on ETI PK.

methodAs part of the French national observational cohort study, therapeutic drug monitoring was performed in 145 wwCF, including 14 pregnant participants. PK profiles for each compound were characterized using the previously published ETI adult population PK model from the same cohort, with model development and evaluation performed using Monolix® software.

resultsA total of 294 plasma samples, including 47 collected from pregnant participants, were drawn during routine clinical care. Pregnancy was found to significantly increase the apparent clearance of tezacaftor (0.97 to 1.44 L/h) and of ivacaftor (9.64 to 11.36 L/h), indicating a decrease in systemic exposure.

conclusionThese findings raise important questions regarding whether decreased total tezacaftor and ivacaftor exposure may compromise the sustained treatment efficacy. The necessity for dose adjustments during pregnancy remains to be evaluated from a PK (unbound ETI concentrations) and pharmacodynamic (clinical effectiveness) perspective, thus warranting further studies.

Indexed as

Chloride Channel AgonistsCystic FibrosisPregnancy ComplicationsAdultAminophenolsBenzodioxolesCohort StudiesDrug CombinationsDrug MonitoringFemaleFranceHumansIndolesModels, BiologicalPregnancyPyrazolesAminophenolsBenzodioxolesChloride Channel AgonistsDrug Combinationselexacaftor, ivacaftor, tezacaftor drug combinationIndolesivacaftorPyrazolesPyridinesPyrrolidinesQuinolinesQuinolonesQuinuclidinestezacaftorcystic fibrosiselexacaftor–tezacaftor–ivacaftorpopulation pharmacokineticspregnancy

Identifiers

PMID42185741
PMCPMC13519782

What OpenQuestion holds

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Registered trials

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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.