Effect of esomeprazole, a proton pump inhibitor on the pharmacokinetics of sonidegib in healthy volunteers.
Br J Clin Pharmacol
; 82(4): 1022-9, 2016 10.
Article
en En
| MEDLINE
| ID: mdl-27277189
ABSTRACT
AIMS:
This study aimed to evaluate the impact of esomeprazole on the pharmacokinetics of sonidegib.METHODS:
This Phase I study evaluated the impact of the proton pump inhibitor (PPI) esomeprazole on the oral absorption and pharmacokinetics (PKs) of a single dose of sonidegib under fasted conditions. A total of 42 healthy subjects were enrolled to receive either sonidegib alone (200 mg single dose) or sonidegib in combination with esomeprazole (40 mg pre-treatment 5 days and combination were given on day 6). Primary PK parameters assessed in the study were area under the concentration-time curve (AUC) from 0-14 days and 0-7 days and maximum observed plasma concentration (Cmax ).RESULTS:
The plasma exposure (AUC0-14d, AUC0-7d and Cmax ) of a single 200 mg oral dose of sonidegib was decreased by 32-38% when sonidegib was co-administered with esomeprazole compared with sonidegib alone, with no apparent change in elimination slope and tmax . Baseline gastric pH was similar between the two arms.CONCLUSIONS:
These results suggest a modest reduction in the extent of sonidegib absorption by esomeprazole. There was no obvious metabolic drug-drug interaction between the two agents. Both sonidegib and esomeprazole were well tolerated in the study population.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Piridinas
/
Compuestos de Bifenilo
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Inhibidores de la Bomba de Protones
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Esomeprazol
Tipo de estudio:
Clinical_trials
Límite:
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
Año:
2016
Tipo del documento:
Article