Variable cellular ivacaftor concentrations in people with cystic fibrosis on modulator therapy.
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.
Palavras-chave
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