[Pharmacokinetics of middle-molecular hydroxyethyl starch (HAS 200/0,5]

The pharmacokinetics of middle molecular weight hydroxyethyl starch (HES; MW 200,000, Mn: 35,000, MW/Mn = 5.71, MS = 0.50) were examined in two groups of normovalaemic subjects. Subjects in group 1 (non-fasted) were administered an approximately equal dose of HES, twice as rapidly as subjects in group 2 (fasted pre- and postinjection). The intravascular half-life (IT50) of HES in groups 1 and 2 was 2.7 +/- 1.3 and 3.9 +/- 1.1 (SD), respectively. 96 h post-injection, 2% of the initially measured HES 200/0.5 concentration remained in the serum of group 1 subjects. The serum glucose level in both groups rose following dosing and remained elevated 12 h post-injection. 24 h post-injection, 66 (group 1) and 50% (group 2) of total infused HES 200/0.5 had been excreted in the urine. In group 2 subjects, the viscosity of the urine measured up to 12 h post-injection, was not significantly affected by the presence of HES 200/0.5. Immediately post-injection in group 1 subjects, the plasma volume was increased an average of 27%, returning to normal baseline values over the next 24 h. The serum alpha-amylase activity rose in group 2 subjects post-injection, concomitantly with a significant reduction in urinary excretion of this enzyme. The molecular size distribution of HES recovered from the intravascular space of group 2 subjects, was distinctly narrower than that of the injected solution and consisted of low molecular size material. Similar changes occurred in the molecular size distribution of HES polymers excreted in the urine of these subjects. The erythrocyte sedimentation rate was not significantly affected by the presence of large quantities of HES 200/0.5 in the blood. The results of this preliminary study in normal man has shown that HES 200/0.5 appears to be an ideal volemic colloid for clinical situations requiring restoration of a diminished plasma volume of short duration.