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Macroamylasaemia following the infusion of low molecular weight-hydroxyethyl starch in man
Abstract:
In fasted normovolaemic subjects dosed with 400 ml of 14% low molecular weight-hydroxyethyl starch (LMW-HES, Mw 264,000 daltons, Mn 63,000 daltons, Mw/Mn = 4.2, MS = 0.43), an increase in the concentration of alpha-amylase was observed in blood which exceeded the upper limit of normal (190 U-1(-1), and in all cases reached twice the basal value. Concomitant with this elevated activity in the blood, the urinary excretion of this enzyme was significantly reduced. Gel filtration of serum recovered from 1 subject on a column of Sephadex G-100 revealed the presence of an LMW-HES-induced macroamylase, detectable for up to 6 h post-injection. This induced alpha-amylase-LMW-HES complex is apparently of a molecular weight that is not easily filtered at the renal glomerulus, thus accounting for the observed hyperamylasaemia concomitant with the decrease in renal excretion. By 12 h post-injection however, the high activity of alpha-amylase in the blood was returning to normal levels and this was observed to parallel the reduction in the formation of macroamylase complexes in serum.
Insights
Low molecular weight-hydroxyethyl starch (LMW-HES) administration in humans can induce a temporary macroamylase complex, leading to elevated blood alpha-amylase and reduced urinary excretion. This complex resolves within 12 hours.
Area of Science:
- Biochemistry
- Pharmacology
- Nephrology
Background:
- Hydroxyethyl starch (HES) is a plasma volume expander.
- Elevated serum alpha-amylase levels can be indicative of various medical conditions.
- Understanding drug-induced biochemical changes is crucial for patient safety.
Purpose of the Study:
- To investigate the effect of low molecular weight-hydroxyethyl starch (LMW-HES) on serum alpha-amylase levels.
- To elucidate the mechanism behind LMW-HES-induced hyperamylasemia.
- To assess the impact of LMW-HES on renal excretion of alpha-amylase.
Main Methods:
- Administration of 400 ml of 14% LMW-HES to fasted, normovolaemic subjects.
- Measurement of serum and urinary alpha-amylase activity.
- Gel filtration chromatography (Sephadex G-100) to analyze serum components.
Main Results:
- LMW-HES administration caused a significant increase in serum alpha-amylase, exceeding normal limits.
- Urinary excretion of alpha-amylase was significantly reduced post-LMW-HES administration.
- Formation of an LMW-HES-induced macroamylase complex was observed, hindering renal filtration.
Conclusions:
- LMW-HES can induce a transient macroamylase complex, causing hyperamylasemia and decreased renal clearance.
- The macroamylase complex formation is responsible for the altered enzyme kinetics.
- Serum alpha-amylase levels and complex formation normalize within 12 hours post-administration.