Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1    Pharmacodynamic properties

Pharmacotherapeutic Group: antihaemorrhagics, blood coagulation factor VIII, ATC code: B02BD02.

Mechanism of action
The factor VIII/von Willebrand factor complex consists of two molecules (factor VIII and von Willebrand factor) with different physiological functions. When infused into a haemophiliac patient, factor VIII binds to von Willebrand factor in the patient’s circulation. Activated factor VIII acts as a cofactor for activated factor IX, accelerating the conversion of factor X to activated factor X. Activated factor X converts prothrombin into thrombin. Thrombin then converts fibrinogen into fibrin and a clot can be formed. Haemophilia A is a sex-linked hereditary disorder of blood coagulation due to decreased levels of factor VIII:C 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 VIII are increased, thereby enabling a temporary correction of the factor deficiency and correction of the bleeding tendencies.

Of note, annualised bleeding rate (ABR) is not comparable between different factor concentrates and between different clinical studies.

In addition to its role as a factor VIII protecting protein, von Willebrand factor mediates platelet adhesion to sites of vascular injury and plays a role in platelet aggregation.

Paediatric population
From clinical trial experience, young children using prophylactic Optivate experienced less bleeds than those only using it on demand. For doses in children see section 4.2.

Pharmacokinetic Properties

5.2    Pharmacokinetic properties
The pharmacokinetics of Optivate have been evaluated in 15 patients (≥ 12 years old) with severe haemophilia A (<2% activity) after bolus doses of 50 IU/kg. The results are presented in the table below:

Parameter                                Mean                    95% CI Non-compartmental terminal half-life     12.4                    10.94-13.83 (hours)
Mean residence time                      17.5                    15.99-18.92 (hours)
Clearance                                3.1                     2.71-3.51 (ml/hour/kg)
Area under curve (AUC 0-48h )            16.1                    13.97-18.28 (IU.h/ml)
Area under curve (AUC 0-inf )            17.31                   14.98-19.65 (IU.h/ml)
Volume of distribution                   53.4                    46.2-60.52 (ml/kg)
Initial (Alpha) half-life                2.2                     1.48-2.88 (hours)
Elimination (Beta) half-life             12.6                    11.33-13.92 (hours)
Incremental recovery                     2.5                     2.22-2.74 (IU/dl per IU/kg)
CI = Confidence Interval

Paediatric population

Pharmacokinetic data are not available in children younger than 12 years old.