Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14C-microtracer and therapeutic dose in cancer patients.
Cancer Chemother Pharmacol
; 81(1): 39-46, 2018 01.
Article
em En
| MEDLINE
| ID: mdl-29043410
ABSTRACT
INTRODUCTION:
Niraparib (Zejula™) is a poly(ADP-ribose) polymerase inhibitor recently approved by the US Food and Drug Administration for the maintenance treatment of patients with recurrent platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. The pivotal phase III clinical trial has shown improved progression-free survival in patients receiving niraparib compared with those receiving placebo.PURPOSE:
Since niraparib is administered orally, it is of interest to investigate the oral bioavailability (F po) of this novel compound, which is the aim of this study.METHODS:
Six patients received an oral therapeutic dose of 300 mg niraparib, followed by a 15-min intravenous infusion of 100 µg 14C-niraparib with a radioactivity of approximately 100 nCi. The niraparib therapeutic dose was measured in plasma using a validated liquid chromatography-tandem mass spectrometry method, whereas the total 14C-radioactivity and 14C-niraparib plasma levels were measured by accelerator mass spectrometry and a validated high performance liquid chromatography assay with AMS.RESULTS:
The F po of niraparib was determined to be 72.7% in humans.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Piperidinas
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Neoplasias da Mama
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Radioisótopos de Carbono
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Neoplasias das Tubas Uterinas
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Inibidores de Poli(ADP-Ribose) Polimerases
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Indazóis
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Antineoplásicos
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adult
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Aged
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Ano de publicação:
2018
Tipo de documento:
Article