生物活性

• 描述Fludarabine Phosphate is the phosphate form of Fludarabine. Fludarabine (2-F-ARAA, 2-fluoro ARA-A) is a chemotherapy drug used in the treatment of chronic lymphocytic leukemia (see https://www.fda.gov/) for targeting on DNA synthesis. It can also work as an inhibitor of stat1 activation. The mechanism of Fludarabine action against to DNA synthesis is similar to other nucleotide analogues. Fludarabine can be phosphorylated to form as the Fludarabine triphosphate and then compete with natural nucleotides to inhibit DNA polymeraseα and incorporate into DNA strand. It can also act on ribonucleotide reductase and thus deplete the dATP pool. Fludarabine can also cause a specific depletion of STAT1, but not of other STATs, as well as cytokine-induced activation of STAT1 and STAT1-dependent gene transcription in lymphocytes.

• 动物研究
  剂量	Mice: 0.3 mg/kg - 0.8 mg/kg[3] (i.p.) Rat: 0.75 mg/kg - 60 mg/kg[4] (i.p.); 20 mg/kg, 75 mg/kg[5] (i.g.)
  给药途径	i.p., i.g.
  动物药代数据	Animal Rats[5] Dogs[5] Dose 20 mg/kg 86.7 mg/m2 Administration i.v. or i.g. i.v. or p.o. F 71.3% (plasma) 100.8 ± 15.4% (p.o.) V 3.20 L/kg (i.v.) T1/2 3.40 h (i.v.) 2.68 h (i.g.) 1.6 - 2.3 h (i.v.) 1.5 - 2.5 h (p.o.) Tmax 0.25 h (i.v.) 1.0 h (i.g.) 0.07 h (i.v.) 0.6 h (p.o.) CL 10.8 ml/min/kg (i.v.) 89 ± 14 ml/min/m2 (i.v.) Cmax 21.9 μM (i.v.) 8.21 μM (i.g.) 20.3 ± 1.0 μM (i.v.) 15.4 ± 3.8 μM (p.o.) AUC 84.2 μM·h (i.v.) 59.9 μM·h (i.g.) 46.2 ± 7.7 μM·h/ml (i.v.) 46.8 ± 11.9 μM·h/ml (p.o.)