The effect of food on the pharmacokinetics of niraparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, in patients with recurrent ovarian cancer

• DOI: 10.1007/s00280-017-3512-5
• Publication Date: 2018-01-10T07:34:05Z
• Authors: Kathleen Moore; Zhi-Yi Zhang; Shefali Agarwal; Howard Burris; Manish R. Patel; Vikram Kansra
• Keywords: Adult; Ovarian Neoplasms; Indazoles; Fasting; Middle Aged; Poly(ADP-ribose) Polymerase Inhibitors; Dietary Fats; 3. Good health; Food-Drug Interactions; 03 medical and health sciences; 0302 clinical medicine; Piperidines; Therapeutic Equivalency; Area Under Curve; Outcome Assessment, Health Care; Humans; Female; Drug Monitoring; Neoplasm Recurrence, Local; Aged

Niraparib is a highly selective inhibitor of PARP-1 and PARP-2 approved in the United States for maintenance treatment of adult patients with recurrent ovarian cancer in complete or partial response to platinum-based chemotherapy. In this open-label crossover study, we evaluated the effects of food on niraparib pharmacokinetics (PK) and safety.Patients received a single 300-mg dose of niraparib either after a high-fat meal or under fasting conditions. After a 7-day PK assessment, all patients received a second 300-mg dose of niraparib under the opposite condition, followed by 7-day PK assessment. Blood samples for PK analyses were collected at baseline (on days 1 and 8) and up to 168 h post-dose. Bioequivalence between conditions was defined by the 90% confidence intervals (CIs) for area under the plasma concentration-time curve (AUC) from 0 to last measurable concentration (AUC0-last) and from 0 to infinity (AUC0-∞) being within the 80-125% range.The high-fat meal/fasting ratios of geometric least-squares means for AUC0-last and AUC0-∞ were 106.8 (90% CI 97.8-116.6) and 110.1 (90% CI 99.7-121.6), respectively, indicating bioequivalence between conditions. Mean half-life, maximum plasma concentration (Cmax), and time to Cmax after the high-fat meal were similar to, 27% smaller than, and 128% greater than after fasting, respectively. Adverse events were similar between conditions.A high-fat meal did not impact the PK profile of niraparib, indicating that niraparib can be taken with or without food. Niraparib was safe and well-tolerated.