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Table 2 Overview of the pharmacokinetic profile of niraparib in preclinical and clinical studies

From: PARP inhibitors as potential therapeutic agents for various cancers: focus on niraparib and its first global approval for maintenance therapy of gynecologic cancers

Description of study population Methods Results References
Patients with ovarian cancer Two-way crossover design ((feeding versus fasting)
- each subject received 2 separate 300-mg doses of niraparib, 1 each in a fasting and a fed state
- investigating pharmacokinetic parameters based on feeding state
- The mean ratios of Cmax and AUC0-inf in the fed (test) versus fasted state (reference) were 0.83 and 1.08, respectively
- The mean t1/2 of feeding and fasting states are 57 and 59 h, respectively
- Median Tmax in the feeding condition is almost 2 times to that of fasting state
Rodents with BRCA2-mutant (Capan-1) and MDA-MB-436 (BRCA-1 mutant) human pancreatic cancer xenograft model Randomized cohorts of Balb/c nude mice bearing either subcutaneous Capan-1 tumors, or intracranial Capan-1-luc tumors
- Dosing of niraparib (15, 30, or 45 mg/kg QD)
- Up to 50 days
- Investigating the brain and plasma levels of niraparib
- Similar Concentration-time profiles of niraparib in the brain and plasma
- Mean brain-to-plasma concentration ratios for niraparib following a single oral dose to rats were 0.85–0.99 of the brain Tmax
- Brain Ctrough levels (24 h) were 2–4 times greater than observed in plasma, indicating niraparib is able to penetrate the brain in rodents
- Have therapeutic benefit in an IC BRCA-mutant human xenograft model
  1. Abbreviations: QD every day, BRCA breast cancer, IC intracranial