[Mathematical decription of the human intravascular elimination of HAS after repeated infusions].

Serum concentrations of high molecular weight-hydroxyethyl starch (HMW-HES, Mw 450,000 d, Mn 71,000 d, Mw/Mn = 6.3, MS = 0.7) were determined in normovolemic subjects dosed with three consecutive daily 500 ml infusions, to mathematically calculate the influence of the two-variable (Mw and MS) HES drug design system, on elimination of this material from the intravascular space under controlled conditions. Following the initial 500 ml (6% solution) infusion, the intravascular clearance up to 24-hours post-injection, was well predicted by the exponential equation: y = 3.94 + 3.34e-0.15x. On days two and three, the clearances up to 24-hours post-injection, were described by the equations: y = 6.32 + 3.75e-0.15x and y = 9.39 + 5.41e-0.15x, respectively. From these mathematical models, it appears that up to 24-hours post-injection on each of the three infusion days, HMW-HES is cleared from the bloodstream in a similar manner. HMW-HES clearance from the blood on day three, however, exhibited a slightly faster rate of decline, as seen by the larger coefficient attributed to the exponential component. The serum concentration of HMW-HES, 480 hours (2.9 weeks) following the third and final infusion, was 2.3 +/- 0.3 (SD) mg ml-1. Thus, in the 480-hour interval following the third and final injection, the serum concentration of HMW-HES measured at 10 minutes after injection 3, had been reduced by 85%. This decline in serum concentration following the infusion of HMW-HES, appears to be greater than previously reported by other investigators.