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

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.

The F _po of niraparib was determined to be 72.7% in humans.

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.

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.