Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a (14)C-microtracer and therapeutic dose in cancer patients

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 (14)C-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 (14)C-radioactivity and (14)C-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.