Pharmacokinetics of Hydroxyethyl Starch (70/0.5) following Repeated Infusions

Abstract

Background: For the purpose of haemodilution different medium substituted hydroxyethyl starches (HES) are available. These plasma substitutes can be further characterized by their average molecular weight (Mw) into medium Mw (HES 200/0.5) and low Mw (HES 70/0.5) starches. Patients and Methods: Pharmacokinetic data were collected in a trial with a design similar to clinical use. 8 healthy volunteers were given 50 g HES on 5 consecutive days (=250 g) to estimate the in vivo changes of the chemical structures of HES (70/0.5). Results: Calculated half-life of serum elimination were 6–10 h which was representative for medium substituted HES and the chosen infusion scheme. The mild accumulation of HES (70/0.5) should be without clinical relevance. The in vivo Mw is equivalent to the in vitro Mw of the infused HES (70/0.5). The in vivo Mw is about 60,000 Dalton for most medium substituted HES. Nevertheless, regarding molar substitution and pattern of substitution (C2:C6) there are some differences between applied HES (70/0.5) and HES recovered in urine. These changes also indicate a shift in the chemical properties of infused HES in the organism. Only 60% of infused HES were recovered in urine. The destination of the remaining 40% (∼100 g in this clinical trial) is still unexplained. A fractional amount might be stored in the reticuloendothelial system. Concerning the measured data of medium substituted HES (70/0.5) it stands to reason that differences in the approximate substituted HES (200/0.5) with a higher molecular weight are without clinical relevance. Conclusion: The in vivo Mw is independent of the in vitro Mw of the applied HES. Pharmacokinetic data suggest that HES (70/0.5) is a good option for the purpose of haemodilution.