Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1.   Pharmacodynamic properties
ATC classification
Pharmacotherapeutic group:
Blood substitutes and plasma protein fractions.
ATC code: B05A A06.

Mechanism of action

Gelaspan 4% B.Braun contains 40 mg/ml of gelatin polysuccinate (also known as succinylated or modified fluid gelatin) with an average molecular weight of 26,500 Daltons in a plasma–adapted, balanced isotonic electrolyte solution. The negative charges introduced into the molecule by succinylation cause an expansion of the molecule; the molecular volume is therefore higher than that of unsuccinylated gelatin of the same molecular weight.
In healthy volunteers, the measured initial volume effect of Gelaspan 4% B.Braun was found to be 80% and 100% of the infused volume with a volume effect over 4 – 5 hours.
The colloid osmotic pressure of the solution determines the initial volume effect.
The duration of the effect depends on clearance of the colloid, which is mainly by renal excretion.
Since the volume effect of Gelaspan 4% B.Braun is equivalent to the administered amount of solution, Gelaspan 4% B.Braun is a plasma substitute and not a plasma expander.
Gelaspan 4% B.Braun also restores the extravascular compartment and does not disturb the electrolyte balance of the extracellular space.
Gelaspan 4% B.Braun contributes to restoration of the electrolyte balance and the correction of an acidosis. Gelaspan 4% B.Braun is lactate-free and may be administered to patients with hepatic disorders. Acetate was added to the solution as a bicarbonate precursor, which can be metabolised in all organs and muscles.

Pharmacodynamic effect
Gelaspan 4% B.Braun replaces the intra- and extravascular volume deficits caused by losses of blood, plasma and interstitial fluid. Thus mean arterial pressure, left-ventricular end-diastolic pressure, cardiac stroke volume, cardiac index, oxygen supply, microcirculation and diuresis are increased by this medicinal product without dehydrating the extravascular space.

Children and adolescents
No studies have been performed in children and adolescents with Gelaspan 4% B.Braun. Therefore, efficacy and safety of Gelaspan 4% B.Braun in children and adolescents cannot be assessed.

Pharmacokinetic Properties

5.2.   Pharmacokinetic properties

Distribution
After infusion, Gelaspan 4% B.Braun is rapidly distributed in the intravascular compartment. There is no evidence that Gelaspan 4% B.Braun is stored in the reticulo-endothelial system or elsewhere in the organism.

Metabolism/Elimination
Most of the infused modified fluid gelatin is excreted via the kidneys. Only a minor amount is excreted in faeces and only approx. 1% is metabolised. The smaller molecules are excreted directly by glomerular filtration, while the larger molecules are probably first degraded proteolytically in the liver and then excreted renally.

Pharmacokinetics in special clinical situations
The plasma half-life of Gelaspan 4% B.Braun may be prolonged in haemodialysis patients (GFR < 0.5 ml/min). However, no accumulation of gelatin is observed.
Gelaspan 4% B.Braun minimizes the risks of dilutional acidosis and rebound alkalosis as observed with lactate-containing solutions infused in patients with liver diseases. Gelaspan 4% B.Braun contains acetate and is lactate-free. It therefore can also be administered to hypovolaemic patients with liver disease.