Accumulation of hydroxyethyl starch (HES) after repeated applications of starches with different molar substitution and similar molecular weight was investigated.
Treatment with five consecutive infusions of hydroxyethyl starch was carried out using two medium molecular weight hydroxyethyl starches with a molar substitution of 0.5 and 0.62. Healthy volunteers received 500 ml 6% HES 200/0.62 (30 g) or 500 ml 10% HES 200/0.5 per day over a period of five consecutive days. Blood samples were taken in the morning before infusions were started (7.A.M.) and at each hour during the infusion period of 4 hours post infusionem until 4 hours after the infusions. During the first 10 days and on the 20th and on the 30th day after the last infusion blood samples were taken.
Both HES solutions were subjectively and objectively well tolerated by healthy volunteers. No side effects were observed. However, pharmacokinetics of the investigated HES-formulations were significantly different. The model-independent calculated elimination half life time (T1/2) increased from day to day. During the five days T1/2 was prolonged for 20 h by high substituted HES (200/0.62) and for 2.5 h for medium substituted HES (200/0.5). The half life times related to the three compartment model calculation were with 0.6 h, 11.6 h and 211 h for HES 200/0.62 two fold higher than the times for HES 200/0.5 with 0.39 h, 6.98 h and 113 h. Plasma clearance for HES 200/0.5 (4.86 ml/min) was five fold higher than that from HES 200/0.62 with 0.98 ml/min. With the exception of the first day of infusion serum concentrations of HES 200/0.5 although only 30 g HES 200/0.6 versus 50 g HES 200/0.5 were infused. No difference of the hemodilution effects between the two HES-formulations were observed. The hemorheologic parameters were similar in both groups with the exception of plasma viscosity which was significantly higher after infusion of HES 200/0.62.
High substituted HES accumulate in serum more than medium substituted HES. Especially when HES must be applied in multiple doses, high substituted HES should not be used or the infusion interval must be adapted to the elimination half life time of the used HES.