Elimination kinetics of different hydroxyethyl starches and effects on blood fluidity

Abstract

In a single blind randomized cross-over study 6 volunteers each received infusions of 500 ml of 6 different types of hydroxyethyl starch (HES) solutions. Between the test periods there was a regular wash-out phase of 3 months. The concentration and molecular weight distribution of the intravascular HES-molecules as well as the blood fluidity were determined before and up to 24 hours after the infusions.

The C2/C6 substitution ratio and the molar substitution exert an essential influence on the elimination of the HES-molecules. An increase in the C2/C6 substitution ratio from 4.6 to 10.8 with unchanged molecular weight (MW) and molar substitution brings about an increase in the half-life of the elimination in the β-phase t1/2-β from 10.4 to 19.5 hours. In case a high C2/C6 substitution ratio is combined with a high molar substitution (0.62 instead of 0.5), half-life rises up to 36.1 hours.

Whereas the molecular weights of all medium-molecular HES-types (MW 200,000) decrease, the medium molecular weight of the low-molecular HES-type (MW 40,000) rises up to 102±9 kDalton after 24 hours. The HES-type with a molar substitution of 0.5 attain a molecular weight ranging between 72±2 and 108±4 kDalton after 24 hours. High-substituted HES (molar substitution of 0.62) in combination with a high substitution ratio showed a MW of 136±8 kDalton and, as such, considerably bigger degradation products.

After the infusion of all HES solutions there is a decrease in haematocrit levels which is most strongly marked with high-substituted HES in combination with a high C2/C6 substitution ratio. Only the solutions with a high C2/C6 substitution ratio produce an increase in plasma viscosity.