Pharmacokinetics of neratinib during coadministration with lansoprazole in healthy subjects.
Br J Clin Pharmacol
; 83(3): 554-561, 2017 03.
Article
em En
| MEDLINE
| ID: mdl-27628584
ABSTRACT
AIMS:
To evaluate the effect of lansoprazole, a proton-pump inhibitor, on the absorption, pharmacokinetics, and safety of neratinib, a pan-HER tyrosine kinase inhibitor, in healthy subjects.METHODS:
This was an open-label, two-period, fixed-sequence study. Fifteen healthy adult subjects received a single oral dose of neratinib 240 mg (Period 1), followed by a washout period, then oral lansoprazole 30 mg once daily for 7 days and a single dose of neratinib 240 mg on Day 5 (Period 2). Pharmacokinetic sampling was performed for 72 h following each neratinib dose. Plasma neratinib concentration-time data were analysed using noncompartmental methods. Geometric mean ratios for AUC0-t , AUC0-inf , and peak plasma concentrations (Cmax ) for neratinib plus lansoprazole vs. neratinib were used to assess the magnitude of the drug-drug interaction if the 90% confidence intervals were outside 80.00-125.00%.RESULTS:
Neratinib geometric least-squares mean (LSM) Cmax was reduced from 84.5 ng ml-1 with neratinib alone to 24.5 ng ml-1 with neratinib plus lansoprazole. The extent of exposure to neratinib was also decreased geometric LSM AUC0-t was 1478 ng ml-1 h with neratinib vs. 426 ng ml-1 h with neratinib plus lansoprazole, and geometric LSM AUC0-inf was 1557 ng ml-1 h vs. 542 ng ml-1 h, respectively. Mean t½ was similar with both treatments (approximately 14 h). Geometric mean ratios 90% confidence intervals for AUC0-t , AUC0-inf and Cmax fell outside the prespecified equivalence range (80.0-125.0%). Treatment-emergent adverse events, all mild, were reported by five (33%) subjects.CONCLUSIONS:
Coadministration of lansoprazole with neratinib reduced the rate and extent of neratinib exposure in healthy subjects.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinolinas
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Interações Medicamentosas
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Lansoprazol
Tipo de estudo:
Clinical_trials
Limite:
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:
Br J Clin Pharmacol
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos