Pharmacokinetic variability of CFTR modulators from standard and alternative regimens.

Autor: Rose NR; Department 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., Chalamalla AR; Department 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., Garcia BA; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, UAB, Birmingham, AL, USA., Krick S; Gregory 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., Bergeron J; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, UAB, Birmingham, AL, USA., Sadeghi H; Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA., Schellhase DE; Department of Pediatrics, Division of Pulmonary and Sleep Medicine, Atrium Health Levine Children's Specialty Center, Charlotte, NC, USA., Ryan KJ; Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, UAB, Birmingham, AL, USA., Dowell AE; Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, UAB, Birmingham, AL, USA., Acosta EP; Gregory Fleming James Cystic Fibrosis Research Center, UAB, Birmingham, AL, USA; Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, UAB, Birmingham, AL, USA., Guimbellot JS; Department 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.
Jazyk: angličtina
Zdroj: Pulmonary pharmacology & therapeutics [Pulm Pharmacol Ther] 2024 Sep; Vol. 86, pp. 102301. Date of Electronic Publication: 2024 May 24.
DOI: 10.1016/j.pupt.2024.102301
Abstrakt: 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.
Competing Interests: Declaration of competing interest Dr. Guimbellot reports consulting fees from Vertex Pharmaceuticals Incorporated, outside the submitted work. All other authors have no conflicts of interest to report.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: