Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1     Pharmacodynamic properties

Pharmacotherapeutic group: antihemorrhagics, blood coagulation factors IX, II, VII, and X in combination, ATC code: B02BD01.

The coagulation factors II, VII, IX and X, which are synthesised in the liver with the help of vitamin K , are commonly called the Prothrombin Complex.

Factor VII is the zymogen of the active serine protease factor VIIa by which the extrinsic pathway of blood coagulation is initiated. The tissue factor-factor VIIa complex activates coagulation factors X and IX, whereby factor IXa and Xa are formed. With further activation of the coagulation cascade prothrombin (factor II) is activated and transformed to thrombin.
By the action of thrombin, fibrinogen is converted to fibrin, which results in clot formation.
The normal generation of thrombin is also of vital importance for platelet function as a part of the primary haemostasis.

Isolated severe deficiency of factor VII leads to reduced thrombin formation and a bleeding tendency due to impaired fibrin formation and impaired primary haemostasis. Isolated deficiency of factor IX is one of the classical haemophilias (haemophilia B). Isolated deficiency of factor II or factor X is very rare but in severe form they cause a bleeding tendency similar to that seen in classical haemophilia.

Acquired deficiency of the vitamin K dependent coagulation factors occurs during treatment with vitamin K antagonists. If the deficiency becomes severe, a severe bleeding tendency results, characterised by retroperitoneal or cerebral bleeds rather than muscle and joint haemorrhage. Severe hepatic insufficiency also results in markedly reduced levels of the vitamin K dependent coagulation factors and a clinical bleeding tendency which, however, is often complex due to a simultaneous ongoing low-grade intravascular coagulation, low platelet levels, deficiency of coagulation inhibitors and disturbed fibrinolysis.

The administration of human prothrombin complex provides an increase in plasma levels of the vitamin K dependent coagulation factors, and can temporarily correct the coagulation defect of patients with deficiency of one or several of these factors.

Pharmacokinetic Properties

5.2     Pharmacokinetic properties
The plasma half-life ranges are:

Coagulation factor           half-life
Factor II              48 - 60 hours
Factor VII              1.5- 6 hours
Factor IX              20 - 24 hours
Factor X               24 - 48 hours

Octaplex 500 IU is administered intravenously and therefore immediately available in the organism.