Gelofusine Mechanism of Action

Pharmacology: Gelofusine is a 4 % w/v solution of succinylated gelatine (also known as modified gelatine in solution) with an average molecular weight of 30 000 daltons (weight average). It has a relative viscosity of 1.9 at 37 °C and a colloid-osmotic pressure of 34 mmHg. The iso-electric point is at pH 4.5. The negative charges introduced into the molecule by succinylation lead to an expansion of the molecule, thus rendering it markedly more voluminous than unsuccinylated protein chains of the same molecular weight.
The characteristics of Gelofusine result in a sufficient volume effect over about 3 - 4 hours.
Therapeutic Effect: Gelofusine substitutes intravascular volume deficits caused by losses of blood or plasma. Thus the mean arterial pressure, the left-ventricular end-diastolic pressure, the cardiac stroke volume, the cardiac index, the oxygen supply and the diuresis are increased.
Mechanism of Action: The colloid-osmotic pressure of the solution determines the extent of its initial volume effect. The duration of the effect depends on the clearance of the colloid by re-distribution and excretion. The volume effect of Gelofusine is equivalent to the administered amount of solution. So Gelofusine is a plasma substitute, it does not have a plasma expanding effect. Lost plasma protein is not substituted by Gelofusine.
Pharmacokinetics: Absorption/Distribution: After infusion, Gelofusine is rapidly distributed in the intravascular but in part - regarding the low molecular weight fraction - also in the interstitial compartment. There is no evidence that Gelofusine is stored in the reticulo-endothelial system or elsewhere in the organism.
Metabolism/elimination: Most of the infused Gelofusine is excreted in urine. Only a minor amount is excreted in faeces and not more than about 1 % is metabolised. The smaller molecules are excreted directly by glomerular filtration while the larger molecules first are degraded proteolytically in the liver and then are also excreted in urine. The proteolytic metabolism is so adaptable that even under the condition of renal insufficiency no accumulation of gelatine is observed. After infusion for plasma volume substitution the half-life time of the intravascular effect of Gelofusine is 4 - 5 hours.
Pharmacokinetics in special clinical situations: The plasma half-life time of Gelofusine may be prolonged in patients on haemodialysis (GFR < 0.5 ml/min).
Toxicology: The toxicological studies on Gelofusine showed that the product is well tolerated. So, the maximum dose of the product is limited by its volume and dilution effects, not by any intrinsic toxicological properties.