Fluzoparib (oral gavage; 0.3, 1, or 3 mg/kg; single dose) exhibits a good pharmacokinetic profile in Female Balb/cA nude mice (5-6 weeks old) mice bearing MDA-MB-436. After a single oral dose, fluzoparib is rapidly absorbed and rapidly cleared from blood at all dose levels; plasma concentrations of fluzoparib quickly reaches maximum within 2 hours. In contrast, concentrations of fluzoparib in tumor remains at high levels even at 24 hours after dosing (57.9 ng/g , 39.3 ng/g, and 85.6 ng/g for doses of 0.3, 1, and 3 mg/kg, respectively)[1].Fluzoparib (oral gavage; 30 mg/kg; 21 days) apparently inhibits the growth of tumor with an inhibition rate of 59% (day 21) at 30 mg/kg, and it does not cause significant loss of body weight in Nude mice bearing MDA-MB-436 (BRCA1-deficient) model[1].Fluzoparib (3mg/kg) combines with Cisplatin, Paclitaxel, or Apatinib (oral gavage; BID; 21 days) causes growth inhibition with rates of 61.4%, 55.3%, and 72.8%, respectively.Fluzoparib, Cisplatin, and Apatinib combination or Fluzoparib, Paclitaxel, and Apatinib combination can cause growth inhibition with rates of 84.9% and 75.6% (day 21), respectively in vivo.The 2-drug combination of Fluzoparib with cisplatin and The 3-drug Fluzoparib, Cisplatin, and Apatinib combination lead to loss of body weight, whereas no apparent toxicity was observed in other combinations[1].
