Urinary excretion kinetics of hydroxyethyl starch 350/0.60 in normovolaemic man

Abstract

Rates of urinary excretion concomitant with the molecular size distribution of filtered polymer fragments were determined in five normovolaemic men dosed with 30 g/m2 BSA of a species of HES (HES 350/0.60) possessing a M-W of 350 000 combined with an MS of 0.60. Approximately 13% of the total injected dose of HES 350/0.60 was excreted in urine 1 hr after dosing, and 45% by 72 hours. Gel filtration of Sepharose CL-4B revealed that aliquots of urine collected 1 hour after injection contained polymer fragments of HES 350/0.60 with values of Kav ranging between 0.88 and 0.84, and possessed a Stokes radius (r = 32A) similar to that of Dextran 20 (M-W 22 700). Polymer fragments of HES 350/0.60 excreted 6 to 48 hours after dosing, however, possessed a Kav ranging between 0.78 and 0.73 with a Stokes radius (r = 45A) similar to that of Dextran 40 (M-W 41 000). All filtered polymer fragments were less polydisperse relative to both the injection solution (Kav 0.60) and residual material recovered from blood immediately after injection (Kav 0.72). These data support the hypothesis that the excretion of HES 350/0.60 occurs in two distinct phases: a rapid phase of elimination dependent on the M-n of the injected solution, and a slower phase dependent on the MS (degree of resistance to alpha-amylase attack). This study, in conjunction with our previous investigation of the changes in circulating HES 350/0.60, define the basic differences between clearance and excretion of the dextrans and of the rapidly degraded species of HES. These data are relevant to the utilisation of HES 350/0.60 during centrifugal leucapheresis.