Determination of the absolute oral bioavailability of niraparib by simultaneous administration of aC-microtracer and therapeutic dose in cancer patients

L van Andel; H. Rosing; Z Zhang; L. Hughes; V Kansra; M Sanghvi; M. Tibben; A. Gebretensae; J H M Schellens; J H Beijnen

doi:10.1007/s00280-017-3455-x

Determination of the absolute oral bioavailability of niraparib by simultaneous administration of aC-microtracer and therapeutic dose in cancer patients

L van Andel
, H. Rosing
, Z Zhang
, L. Hughes
, V Kansra
, M Sanghvi
, M. Tibben
, A. Gebretensae
, J H M Schellens
, J H Beijnen

Department of Pharmacy and Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute and MC Slotervaart, PO Box 90440, 1006 BK, Amsterdam, The Netherlands. [email protected].
Department of Pharmacy and Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute and MC Slotervaart, PO Box 90440, 1006 BK, Amsterdam, The Netherlands.
TESARO, Inc., Waltham, MA, USA.
Xceleron, Inc., A Pharmaron Company, Germantown, MD, USA.
Netherlands Cancer Institute

Research output: Contribution to journal › Article › Academic › peer-review

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 (Fpo) 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 µg14C-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 total14C-radioactivity and14C-niraparib plasma levels were measured by accelerator mass spectrometry and a validated high performance liquid chromatography assay with AMS.

RESULTS: The Fpoof niraparib was determined to be 72.7% in humans.

Original language	English
Pages (from-to)	39-46
Number of pages	8
Journal	Cancer Chemotherapy and Pharmacology
Volume	81
Issue number	1
Early online date	17 Oct 2017
DOIs	https://doi.org/10.1007/s00280-017-3455-x
Publication status	Published - Jan 2018

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Niraparib
Bioavailability
AMS
LC-MS/MS
Pharmacokinetics
14C-microtracer

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10.1007/s00280-017-3455-x

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van Andel, L., Rosing, H., Zhang, Z., Hughes, L., Kansra, V., Sanghvi, M., Tibben, M., Gebretensae, A., Schellens, J. H. M., & Beijnen, J. H. (2018). Determination of the absolute oral bioavailability of niraparib by simultaneous administration of aC-microtracer and therapeutic dose in cancer patients. Cancer Chemotherapy and Pharmacology, 81(1), 39-46. https://doi.org/10.1007/s00280-017-3455-x

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title = "Determination of the absolute oral bioavailability of niraparib by simultaneous administration of aC-microtracer and therapeutic dose in cancer patients",

abstract = "INTRODUCTION: Niraparib (Zejula{\texttrademark}) 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 (Fpo) 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 µg14C-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 total14C-radioactivity and14C-niraparib plasma levels were measured by accelerator mass spectrometry and a validated high performance liquid chromatography assay with AMS.RESULTS: The Fpoof niraparib was determined to be 72.7\% in humans.",

keywords = "Niraparib, Bioavailability, AMS, LC-MS/MS, Pharmacokinetics, 14C-microtracer",

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van Andel, L, Rosing, H, Zhang, Z, Hughes, L, Kansra, V, Sanghvi, M, Tibben, M, Gebretensae, A, Schellens, JHM & Beijnen, JH 2018, 'Determination of the absolute oral bioavailability of niraparib by simultaneous administration of aC-microtracer and therapeutic dose in cancer patients', Cancer Chemotherapy and Pharmacology, vol. 81, no. 1, pp. 39-46. https://doi.org/10.1007/s00280-017-3455-x

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T1 - Determination of the absolute oral bioavailability of niraparib by simultaneous administration of aC-microtracer and therapeutic dose in cancer patients

AU - van Andel, L

AU - Rosing, H.

AU - Zhang, Z

AU - Hughes, L.

AU - Kansra, V

AU - Sanghvi, M

AU - Tibben, M.

AU - Gebretensae, A.

AU - Schellens, J H M

AU - Beijnen, J H

PY - 2018/1

Y1 - 2018/1

N2 - 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 (Fpo) 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 µg14C-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 total14C-radioactivity and14C-niraparib plasma levels were measured by accelerator mass spectrometry and a validated high performance liquid chromatography assay with AMS.RESULTS: The Fpoof niraparib was determined to be 72.7% in humans.

AB - 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 (Fpo) 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 µg14C-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 total14C-radioactivity and14C-niraparib plasma levels were measured by accelerator mass spectrometry and a validated high performance liquid chromatography assay with AMS.RESULTS: The Fpoof niraparib was determined to be 72.7% in humans.

KW - Niraparib

KW - Bioavailability

KW - AMS

KW - LC-MS/MS

KW - Pharmacokinetics

KW - 14C-microtracer

U2 - 10.1007/s00280-017-3455-x

DO - 10.1007/s00280-017-3455-x

M3 - Article

C2 - 29043410

SN - 0344-5704

VL - 81

SP - 39

EP - 46

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

IS - 1

ER -

Determination of the absolute oral bioavailability of niraparib by simultaneous administration of aC-microtracer and therapeutic dose in cancer patients

Abstract

UN SDGs

Keywords

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