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Variable cellular ivacaftor concentrations in people with cystic fibrosis on modulator therapy.
Guimbellot, Jennifer S; Ryan, Kevin J; Anderson, Justin D; Liu, Zhongyu; Kersh, Latona; Esther, Charles R; Rowe, Steven M; Acosta, Edward P.
Afiliação
  • Guimbellot JS; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham (UAB), Birmingham, AL, United States; Department of Pediatrics, Division of Pulmonary and Sleep Medicine, UAB, Birmingham, AL, United States. Electronic address: jguimbellot@peds.uab.edu.
  • Ryan KJ; Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, UAB, Birmingham, AL, United States.
  • Anderson JD; Department of Pediatrics, Division of Pulmonary and Sleep Medicine, UAB, Birmingham, AL, United States.
  • Liu Z; Department of Pediatrics, Division of Pulmonary and Sleep Medicine, UAB, Birmingham, AL, United States.
  • Kersh L; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham (UAB), Birmingham, AL, United States.
  • Esther CR; Marsico Lung Institute, University of North Carolina, Chapel Hill, NC, United States.
  • Rowe SM; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham (UAB), Birmingham, AL, United States; Department of Pediatrics, Division of Pulmonary and Sleep Medicine, UAB, Birmingham, AL, United States; Departments of Medicine and Cell Developmental and Integrative Biol
  • Acosta EP; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham (UAB), Birmingham, AL, United States; Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, UAB, Birmingham, AL, United States.
J Cyst Fibros ; 19(5): 742-745, 2020 09.
Article em En | MEDLINE | ID: mdl-32044246
The development of CFTR modulators has transformed the care of patients with cystic fibrosis (CF). Although the clinical efficacy of modulators depends on their concentrations in target tissues, the pharmacokinetic properties of these drugs in epithelia are not utilized to guide patient care. We developed assays to quantitate ivacaftor in cells and plasma from patients on modulator therapy, and our analyses revealed that cellular ivacaftor concentrations differ from plasma concentrations measured concurrently, with evidence of in vivo accumulation of ivacaftor in the cells of patients. While the nature of this study is exploratory and limited by a small number of patients, these findings suggest that techniques to measure modulator concentrations in vivo will be essential to interpreting their clinical impact, particularly given the evidence that ivacaftor concentrations influence the activity and stability of restored CFTR protein.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Quinolonas / Fibrose Cística / Células Epiteliais / Agonistas dos Canais de Cloreto / Aminofenóis Limite: Humans Idioma: En Revista: J Cyst Fibros Ano de publicação: 2020 Tipo de documento: Article País de publicação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Quinolonas / Fibrose Cística / Células Epiteliais / Agonistas dos Canais de Cloreto / Aminofenóis Limite: Humans Idioma: En Revista: J Cyst Fibros Ano de publicação: 2020 Tipo de documento: Article País de publicação: Holanda