Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties

Pharmacotherapeutic group: antihaemorrhagics, blood coagulation factor IX.
ATC code: B02B D04

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 are increased, thereby enabling a temporary correction of the factor deficiency and correction of the bleeding tendencies.

When reconstituted as recommended (see section 6.6), the resulting solution is a clear, colourless, isotonic preparation of neutral pH, containing approximately 100 times the factor IX activity found in an equal volume of plasma.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties

Short term infusion of Mononine in 38 patients with haemophilia B (recovery study) revealed a mean incremental recovery of 1.71 IU/dl per IU/kg b.w. (range 0.85-4.66). Mean terminal half-life in a subgroup of 28 patients was 14.9 hours (range 7.2 to 22.7).

Pharmacokinetic data of Mononine was also determined in 12 patients (elective surgery) prior to treatment with continuous infusion of Mononine.

Parameter                              Recovery study (n=38)             Elective surgery (n=12) Mean (range)                       Mean (range)
Incremental recovery                      1.71 (0.85-4.66)                  1.21 (0.83-1.60) (IU/dl per IU/kg)
Terminal half-life (h)                    14.9 (7.2-22.7)++                   16.4 (8.7-36.6) Initial half-life+++ (h)                         n.a.                         2.46 (0.34-6.2) Area under the curve+                            n.a.                      0.254 (0.147-0.408) (h × kg/ml)
Volume at steady state                            n.a.                         111 (77-146) (ml/kg)
Clearance (ml/h/kg)                               n.a.                       4.27 (2.45-6.78) Mean residence time (h)                           n.a.                       27.4 (17.7-42.6) + Standardized to 1 IU/kg of dose            n.a.: not available
++ Based on a subgroup of 28 patients
+++ Data from only 4 of the 12 patients. The remaining 8 patients followed a simple one-compartment model.
A distribution process of Mononine is thus observed only occasionally.

Paediatric population
No pharmacokinetic data are available in patients younger than 12 years.