Keith J C, Ferranti T J, Misra B, Frederick T, Rup B, McCarthy K, Faulkner R, Bush L, Schaub R G
Department of Preclinical Research, Genetics Institute, Inc., Cambridge, MA 02140, USA.
Thromb Haemost. 1995 Jan;73(1):101-5.
The pharmacokinetics of intravenously administered recombinant human factor IX (rhFIX) were studied in Sprague-Dawley rats and Beagle dogs. Rats received rhFIX (50 IU/kg once daily) for 28 days, and the plasma half-life was 5 h. Anti-Human Factor IX serum antibody levels were found in only 1 of 12 rats. The pharmacokinetic profiles of rhFIX or Mononine, a purified human plasma-derived factor IX, after single 100 IU/kg i.v. doses in dogs, were similar. Peak plasma concentrations of rhFIX and Mononine were 4-5 micrograms/ml. The mean plasma half-lives were 13.2 +/- 1.6 h for rhFIX and 13.3 +/- 1.6 h for Mononine. Dogs also received rhFIX (40 IU/kg i.v., daily) for 28 days or Mononine (40 IU/kg i.v. daily) for 14 days. Anti-human Factor IX serum antibody levels were determined for each compound. Pharmacokinetic half-lives decreased in these treated dogs which developed antihuman Factor IX antibodies. The antibody responses in 28 day rhFIX (40 IU/kg) dogs were similar to 14 day Mononine (40 IU/kg) dogs.
在斯普拉格-道利大鼠和比格犬中研究了静脉注射重组人凝血因子IX（rhFIX）的药代动力学。大鼠接受rhFIX（50 IU/kg，每日一次），持续28天，血浆半衰期为5小时。在12只大鼠中，仅1只检测到抗人凝血因子IX血清抗体水平。在犬单次静脉注射100 IU/kg剂量后，rhFIX或纯化的人血浆源性凝血因子IX（莫罗奈宁）的药代动力学特征相似。rhFIX和莫罗奈宁的血浆峰值浓度为4-5微克/毫升。rhFIX的平均血浆半衰期为13.2±1.6小时，莫罗奈宁为13.3±1.6小时。犬还接受rhFIX（40 IU/kg，静脉注射，每日一次），持续28天，或莫罗奈宁（40 IU/kg，静脉注射，每日一次），持续14天。测定了每种化合物的抗人凝血因子IX血清抗体水平。在产生抗人凝血因子IX抗体的这些治疗犬中，药代动力学半衰期缩短。28天接受rhFIX（40 IU/kg）治疗的犬与14天接受莫罗奈宁（40 IU/kg）治疗的犬的抗体反应相似。
