Pharmacokinetic variability of CFTR modulators from standard and alternative regimens.
Pulm Pharmacol Ther
; 86: 102301, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-38797221
ABSTRACT
Elexacaftor, tezacaftor, ivacaftor (ETI) is a CFTR modulator combination approved for use in â¼90 % 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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinolonas
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Regulador de Condutância Transmembrana em Fibrose Cística
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Fibrose Cística
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Combinação de Medicamentos
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Benzodioxóis
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Espectrometria de Massas em Tandem
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Aminofenóis
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Indóis
Idioma:
En
Revista:
Pulm Pharmacol Ther
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos