Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1         Pharmacodynamic properties

Pharmacotherapeutic group: antihemorrhagics: blood coagulation factor IX ATC-code: B02BD04
Factor IX is a single chain glycoprotein with a molecular mass of about 68,000 Dalton. It is a vitamin-K dependent coagulation factor and it is synthesised in the liver. Factor IX is activated by factor XIa in the intrinsic coagulation pathway, and by the factor VII/tissue factor complex in the extrinsic pathway. Activated factor IX, in combination with activated factor VIII, activates factor X. Activated factor X converts prothrombin into thrombin.
Thrombin then converts fibrinogen into fibrin and a clot is formed.
Haemophilia B is a sex-linked hereditary disorder of blood coagulation due to decreased levels of factor IX and results in profuse bleeding into joints, muscles or internal organs, either spontaneously or as a result of accidental or surgical trauma. By replacement therapy the plasma levels of factor IX is increased, thereby enabling a temporary correction of the factor deficiency and correction of the bleeding tendencies.

Paedriatric population
A study in 25 children below 6 years of age was conducted. Thereof, 6 patients were previously untreated. The recovery after administration of >25 IU of OCTANINE F/kg body weight was investigated during the first 3 months of treatment and after 12-24 months. The incremental recovery (geometric mean ± s.d., one-stage assay, actual potency) was calculated to be 0.8±1.4 and 0.9±1.3 %/IU/kg at the 1st and the 2nd assessment, respectively.

Pharmacokinetic Properties

5.2    Pharmacokinetic properties

For OCTANINE F the following results were achieved in one pharmacokinetic study with 13 Haemophilia B patients over 12 years of age (mean age 28 years, range 12-61 years): 
N=13                              Median       Mean       SD*       Minimum      Maximum Incremental Recovery               1.2          1.3       0.5         0.8          2.4 [IU/dl]/[IU/kg]

AUC*norm                              32.4     37.7       13.0         24.5         64.0 (IU x dl-1 x h x IU-1 x kg)

Half-life (h)                         27.8     29.1        5.2         22.0         36.8 MRT* (h)                              39.4     40.0        7.3         30.2         51.6 Clearance (ml x h-1 x kg)              3.1      2.9        0.9          1.6          4.1 *AUC = area under the curve
*MRT = mean residence time
*SD  = standard deviation

The incremental recovery was also tested in a second study. The meta-analysis of all recovery assessments (n=19) resulted in a mean recovery of 1.1 [IU/dl]/[IU/kg].