Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties

Pharmacotherapeutic group: immune sera and immunoglobulins: immunoglobulins, normal human, for intravascular administration, ATC code: J06BA02

Human normal immunoglobulin contains mainly immunoglobulin G (IgG) with a broad spectrum of antibodies against infectious agents.

Human normal immunoglobulin contains the IgG antibodies present in the normal population.
It is usually prepared from pooled plasma from not fewer than 1000 donations. It has a distribution of immunoglobulin G subclasses closely proportional to that in native human plasma. Adequate doses of of this medicinal product may restore abnormally low immunoglobulin G levels to the normal range.

The mechanism of action in indications other than replacement therapy is not fully elucidated, but includes immunomodulatory effects.

Paediatric population

There are no theoretical or observed differences in the action of immunoglobulins in children compared to adults.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties

Human normal immunoglobulin is immediately and completely bioavailable in the recipient’s circulation after intravenous administration. It is distributed relatively rapidly between plasma and extravascular fluid; after approximately 3 to 5 days equilibrium is reached between the intra- and extravascular compartments.

Pharmacokinetic parameters for KIOVIG were determined in the two clinical studies in PID patients performed in Europe and the US. In these studies, a total of 83 subjects at least 2 years of age were treated with doses of 300 to 600 mg/kg body weight every 21 to 28 days for 6 to 12 months. The median IgG half-life after administration of KIOVIG was 32.5 days. This half- life may vary from patient to patient, in particular in primary immunodeficiency.
Pharmacokinetic parameters for the product are summarized in the table below. All parameters were analysed separately for three age groups, children (below 12 years, n=5), adolescents (13 to 17 years, n=10), and adults (above 18 years of age, n=64). The values obtained in the studies are comparable to parameters reported for other human immunoglobulins.

Summary of KIOVIG pharmacokinetic parameters
Children                Adolescents                       Adults
Parameter                 (12 years or below)     (13 to 17 years)                  (18 years or above) Median 95% CI*          Median 95% CI                     Median 95% CI Terminal half-life (days)   41.3     20.2 to 86.8   45.1     27.3 to 89.3             31.9     29.6 to 36.1 Cmin (mg/dl)/(mg/kg)
2.28     1.72 to 2.74   2.25     1.98 to 2.64            2.24      1.92 to 2.43 (trough level)
Cmax (mg/dl)/(mg/kg)
4.44     3.30 to 4.90   4.43     3.78 to 5.16            4.50      3.99 to 4.78 (peak level)
In-vivo recovery (%)        121      87 to 137      99       75 to 121               104       96 to 114 Incremental     recovery
2.26     1.70 to 2.60   2.09     1.78 to 2.65            2.17      1.99 to 2.44 (mg/dl)/(mg/kg)
AUC0-21d (g·h/dl) (area
1.49     1.34 to 1.81   1.67     1.45 to 2.19            1.62      1.50 to 1.78 under the curve)
*CI – Confidence Interval

IgG and IgG-complexes are broken down in cells of the reticuloendothelial system.