[Intravascular persistence, tissue storage and excretion of hydroxyethyl starch (HAS)]

Area of Science:

• Biochemistry
• Pharmacology
• Resuscitation Medicine

Background:

• Hydroxyethyl starch (HES) is derived from amylopectin, a glucose polymer.
• Hydroxyethylation modifies HES, retarding its hydrolysis by amylase.
• HES is investigated as a potential plasma volume expander.

Purpose of the Study:

• To evaluate the intravascular persistence and excretion kinetics of hydroxyethyl starch.
• To compare the behavior of HES with other plasma substitutes like Dextran 70.
• To assess the tissue distribution and elimination characteristics of HES.

Main Methods:

• Hydroxyethylation of amylopectin to produce HES with 70-90% substitution.
• Administration of HES (435,000 molecular weight) and Dextran 70 to study pharmacokinetic parameters.
• Analysis of intravascular persistence, urinary excretion, and tissue storage (reticuloendothelial, hepatic, renal cells).

Main Results:

• HES exhibits intravascular persistence and urinary excretion kinetics similar to Dextran 70.
• Both HES and Dextran 70 are briefly stored in reticuloendothelial and hepatic cells.
• Renal tubules show swelling and vacuolation, but renal function remains largely unaltered.
• Elimination of HES from tissue storage sites is significantly faster than non-metabolized polymers like acacia and polyvinylpyrrolidone.

Conclusions:

• The distribution and excretion kinetics of hydroxyethyl starch are suitable for its use as a plasma substitute.
• HES demonstrates favorable pharmacokinetic properties compared to older plasma expanders.
• Further clinical evaluation is warranted to confirm the safety and efficacy of HES in plasma volume expansion.