19F-NMR-based determination of the absorption, metabolism and excretion of the oral phosphatidylinositol-3-kinase (PI3K) delta inhibitor leniolisib (CDZ173) in healthy volunteers.
Xenobiotica
; 49(8): 953-960, 2019 Aug.
Article
em En
| MEDLINE
| ID: mdl-30215545
ABSTRACT
1. Leniolisib is a novel oral phosphatidylinositol-3-kinase (PI3K) delta inhibitor, currently in clinical development for the treatment of inflammatory and autoimmune diseases. 2. We investigated the absorption, metabolism, and excretion of leniolisib in healthy subjects after a single oral 400 mg dose as part of a first-in-human clinical study. The parent drug and metabolites were quantified by 19F-NMR in plasma, urine and faeces after liquid chromatography separation, and structures were determined by liquid chromatography coupled to tandem mass spectrometry. 3. Drug-related material was mainly excreted as oxidative metabolites in urine and faeces, providing evidence that elimination occurs mainly by metabolism. No metabolites were abundant in plasma relative to the parent drug. An average mass balance of 66% was obtained, demonstrating that relatively extensive elimination/excretion data can be obtained by 19F-NMR in a first in human clinical study without the use of a radiolabeled drug.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piridinas
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Pirimidinas
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Espectroscopia de Ressonância Magnética
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Inibidores de Proteínas Quinases
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Voluntários Saudáveis
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Absorção Fisiológica
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Flúor
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Inibidores de Fosfoinositídeo-3 Quinase
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
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Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Xenobiotica
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Suíça