Evidence map›Paper›PMID 38797221›Full record

ArticlePulmonary pharmacology & therapeutics2024

Pharmacokinetic variability of CFTR modulators from standard and alternative regimens.

Natalie R Rose, Ashritha R Chalamalla, Bryan A Garcia, Stefanie Krick, Jonathan Bergeron, Hossein Sadeghi, Dennis E Schellhase, Kevin J Ryan, Alexander E Dowell, Edward P Acosta and 1 more

Abstract read
In one paragraph

Article in Pulmonary pharmacology & therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
–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

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Observational
  4. Article
  5. Observational
  6. 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

11 authors.

Natalie R RoseDepartment of Pediatrics, Division of Pulmonary and Sleep Medicine, University of Alabama at Birmingham (UAB), Birmingham, AL, USA; Gregory Fleming James Cystic Fibrosis Research Center, UAB, Birmingham, AL, USA.
Ashritha R ChalamallaDepartment of Pediatrics, Division of Pulmonary and Sleep Medicine, University of Alabama at Birmingham (UAB), Birmingham, AL, USA; Gregory Fleming James Cystic Fibrosis Research Center, UAB, Birmingham, AL, USA.
Bryan A GarciaDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, UAB, Birmingham, AL, USA.
Stefanie KrickGregory Fleming James Cystic Fibrosis Research Center, UAB, Birmingham, AL, USA; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, UAB, Birmingham, AL, USA.
Jonathan BergeronDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, UAB, Birmingham, AL, USA.
Hossein SadeghiDepartment of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.
Dennis E SchellhaseDepartment of Pediatrics, Division of Pulmonary and Sleep Medicine, Atrium Health Levine Children's Specialty Center, Charlotte, NC, USA.
Kevin J RyanDepartment of Pharmacology and Toxicology, Division of Clinical Pharmacology, UAB, Birmingham, AL, USA.
Alexander E DowellDepartment of Pharmacology and Toxicology, Division of Clinical Pharmacology, UAB, Birmingham, AL, USA.
Edward P AcostaGregory Fleming James Cystic Fibrosis Research Center, UAB, Birmingham, AL, USA; Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, UAB, Birmingham, AL, USA.
Jennifer S GuimbellotDepartment of Pediatrics, Division of Pulmonary and Sleep Medicine, University of Alabama at Birmingham (UAB), Birmingham, AL, USA; Gregory Fleming James Cystic Fibrosis Research Center, UAB, Birmingham, AL, USA; Department of Pediatrics, Section of Pulmonary and Sleep Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Electronic address: jguimbellot@uams.edu.

Funding

National Dissemination of I-Corps@NCATS: Accelerating Translation through CommercializationUL1TR003096 · NCATS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GUTIERREZ, ORLANDO M, KIMBERLY, ROBERT P. · 2019 to 2023
$43.6M
UAB CF Research and Translation Core CenterP30DK072482 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI George Martin Solomon · 2007 to 2026
$23.0M
Translational Program in CFTR-Related Airway DiseasesR35HL135816 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ROWE, STEVEN MARK · 2017 to 2022
$6.3M
Pharmacometric approaches to precision optimization of ivacaftor response in cystic fibrosis patientsK23HL143167 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GUIMBELLOT, JENNIFER S · 2020 to 2024
$839k
NCATS NIH HHS UL1 TR003096NHLBI NIH HHS K23 HL143167NHLBI NIH HHS R35 HL135816NIDDK NIH HHS P30 DK072482
6 · The paper itself

Abstract

Elexacaftor, tezacaftor, ivacaftor (ETI) is a CFTR modulator combination approved for use in ∼90 % of people with cystic fibrosis (pwCF) over 2 years old. While most pwCF tolerate this therapy well, some are intolerant to standard dosing, and others show little response. Clinical providers may adjust ETI dosing to combat these issues, but these adjustments are not well guided by pharmacokinetic evidence. Our post-approval study aimed to describe pharmacokinetic variability of ETI plasma concentrations in 15 participants who were administered a standard or reduced dose. ETI were quantified by LC-MS/MS in plasma samples taken prior to the morning dose. Results showed non-significant differences for each compound regardless of dosing regimen and after dose equivalence normalization. The majority of participants in both dosing groups had concentrations expected to elicit clinical response to ETI therapy. These findings indicate that dose reduction may be a viable strategy to maintain clinical benefit while managing intolerance.

Indexed as

AminophenolsBenzodioxolesCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDrug CombinationsIndolesQuinolonesTandem Mass SpectrometryAdolescentAdultChloride Channel AgonistsChromatography, LiquidDose-Response Relationship, DrugFemaleHumansMaleAminophenolsBenzodioxolesCFTR protein, humanChloride Channel AgonistsCystic Fibrosis Transmembrane Conductance RegulatorDrug Combinationselexacaftor, ivacaftor, tezacaftor drug combinationIndolesivacaftorPyrazolesPyridinesPyrrolesQuinolinesQuinolonesCystic fibrosisElexacaftorIvacaftorLC-MS/MSPharmacokineticsTezacaftor

Identifiers

PMID38797221
PMCPMC12077763

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.