Changes in the molecular size distribution and post-transfusion survival of hydroxyethyl starch 350/0.60 as influenced by a lower degree of hydroxyethylation: a study in normal man.
The need to provide a greater rate of colloid clearance from blood than is presently available with the long-acting dosage form of HES 450/0.70 prompted the clinical investigation of a new species of hydroxyethyl starch (HES) possessing a M-w of 350000 concomitant with a molar substitution of 0.60 (HES 350/0.60). The concentration of HES 350/0.60 in serum fell to half its peak value in 10.2 +/- 0.7 (SD) hour (in contrast to an IT50 of approximately 25 hours with HES 450/0.70). Levels of glucose in serum remained elevated in normal fasted subjects after dosing, suggesting that catabolism of the infused HES 350/0.60 was occurring. Hydrolysis of residual HES 350/0.60 was confirmed by Sepharose CL-4B gel filtration analysis of material obtained from serum, showing continual production of smaller molecules relative to the injected solution (in contrast to HES 450/0.70, in which intermediate polymer fragments are recovered). Recovered HES 350/0.60 material displayed a Kav ranging between 0.74 and 0.72 and possessed a Stokes radius (r = 45A) similar to that of dextran 40 (M-w 41000). HES 350/0.69 appears to offer the same advantages as the currently available long-acting HES 450/0.70 but is removed from blood approximately twice as rapidly. This more rapid hydrolysis of HEs 350/0.60 may be useful, for example, in avoiding cumulative build-up of colloid in the blood of normal donors undergoing consecutive leucapheresis procedures.
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001803:Blood Transfusion; D003102:Colloids; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000097:blood*; D008297:Male; D008970:Molecular Weight; D013213:Starch / Q000031:analogs & derivatives*
D001786:Blood Glucose; D003102:Colloids; D006895:Hydroxyethyl Starch Derivatives; D013213:Starch