Assessment of drug-drug interaction potential between ceritinib and proton pump inhibitors in healthy subjects and in patients with ALK-positive non-small cell lung cancer.
Cancer Chemother Pharmacol
; 79(6): 1119-1128, 2017 Jun.
Article
en En
| MEDLINE
| ID: mdl-28424965
ABSTRACT
PURPOSE:
The impact of proton pump inhibitors (PPIs) on the pharmacokinetics (PK) and efficacy of ceritinib was evaluated.METHODS:
A healthy subject drug-drug interaction (DDI) study was conducted to assess the effect of esomeprazole on the PK of a single 750 mg dose of ceritinib. To further investigate the impact of PPIs on the PK and efficacy of ceritinib in ALK-positive cancer patients, two subgroup analyses were performed. Analysis 1 evaluated ceritinib steady-state trough concentration (Ctrough,ss) and overall response rate (ORR) by concomitant use of PPIs in patients from the ASCEND-1, -2, and -3 studies; analysis 2 evaluated ceritinib single-dose and steady-state AUC0-24h and C max by concomitant PPI use in patients from ASCEND-1 using a definition of PPI usage similar to that used in the healthy subject study.RESULTS:
In the healthy subject study, co-administration of a single 750 mg dose of ceritinib with esomeprazole 40 mg for 6 days decreased ceritinib AUC0-∞ by 76% and C max by 79%. However, based on subgroup analysis 1, patients had similar C trough,ss and ORR regardless of concomitant PPI usage. Based on analysis 2, co-administration of a single 750 mg ceritinib dose with PPIs for 6 days in patients suggested less effect on ceritinib exposure than that observed in healthy subjects as AUC0-24h decreased by 30% and C max decreased by 25%. No clinically meaningful effect on steady-state exposure was observed after daily dosing.CONCLUSIONS:
Long-term administration of ceritinib with PPIs does not adversely affect the PK and efficacy of ceritinib in ALK-positive cancer patients.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Pirimidinas
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Sulfonas
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Proteínas Tirosina Quinasas Receptoras
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Carcinoma de Pulmón de Células no Pequeñas
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Inhibidores de Proteínas Quinasas
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Inhibidores de la Bomba de Protones
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Esomeprazol
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Neoplasias Pulmonares
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Antineoplásicos
Tipo de estudio:
Prognostic_studies
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
Revista:
Cancer Chemother Pharmacol
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos