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Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14C-microtracer and therapeutic dose in cancer patients.
van Andel, L; Rosing, H; Zhang, Z; Hughes, L; Kansra, V; Sanghvi, M; Tibben, M M; Gebretensae, A; Schellens, J H M; Beijnen, J H.
Afiliación
  • van Andel L; Department of Pharmacy and Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute and MC Slotervaart, PO Box 90440, 1006 BK, Amsterdam, The Netherlands. l.v.andel@nki.nl.
  • Rosing H; Department of Pharmacy and Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute and MC Slotervaart, PO Box 90440, 1006 BK, Amsterdam, The Netherlands.
  • Zhang Z; TESARO, Inc., Waltham, MA, USA.
  • Hughes L; TESARO, Inc., Waltham, MA, USA.
  • Kansra V; TESARO, Inc., Waltham, MA, USA.
  • Sanghvi M; Xceleron, Inc., A Pharmaron Company, Germantown, MD, USA.
  • Tibben MM; Department of Pharmacy and Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute and MC Slotervaart, PO Box 90440, 1006 BK, Amsterdam, The Netherlands.
  • Gebretensae A; Department of Pharmacy and Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute and MC Slotervaart, PO Box 90440, 1006 BK, Amsterdam, The Netherlands.
  • Schellens JHM; Division of Clinical Pharmacology, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Beijnen JH; Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Cancer Chemother Pharmacol ; 81(1): 39-46, 2018 01.
Article en En | MEDLINE | ID: mdl-29043410
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Piperidinas / Neoplasias de la Mama / Radioisótopos de Carbono / Neoplasias de las Trompas Uterinas / Inhibidores de Poli(ADP-Ribosa) Polimerasas / Indazoles / Antineoplásicos Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Cancer Chemother Pharmacol Año: 2018 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Piperidinas / Neoplasias de la Mama / Radioisótopos de Carbono / Neoplasias de las Trompas Uterinas / Inhibidores de Poli(ADP-Ribosa) Polimerasas / Indazoles / Antineoplásicos Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Cancer Chemother Pharmacol Año: 2018 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Alemania