Pharmacokinetics of Hydroxyethyl Starch in Normal Subjects

Abstract

To determine the elimination of high-molecular-weight hydroxyethyl starch (HES, Mw 450,000) in normal subjects, ten volunteers were given 500 ml 6% HES solution by intravenous infusion, and serial blood and urine samples were collected for nonglucose total carbohydrate determination. On the average, 46 and 64 per cent of the dose was excreted in the urine within two and eight days, respectively. The plasma concentration declined rapidly during the first week after infusion. The average terminal half-life was 17 days during the first 42 days, which accounted for elimination of about 90 per cent of the dose. The remainder was eliminated with a terminal half-life of 48 days determined between days 42 and 83 of the study. As expected, the infusion of HES resulted in plasma volume expansion over a 48-hour period during which time levels of nonglucose carbohydrates were above 3.5 mg/ml. HES is metabolized by alpha-amylase in the body. During the first 48 hours after infusion of HES, plasma alpha-amylase activity was significantly increased over control. Concomitantly, alpha-amylase activity in urine was also elevated but not significantly so.

Hetastarch: An Overview of the Colloid and its Metabolism

“…Using an assay that measures reducing sugars formed by amylase action" rather than disappearance of an added substrate.v:" it was shown that the urinary level of ex-amylase is not decreased, but in reality, slightly increased. 34 These data suggested the possibility of another mechanism, perhaps as simple as an increased release of ex-amylase from various tissues, as a result of the presence of HES in the body.…”

“…12 Figure 2 depicts typical average plasma concentrations and urinary excretion rate vs. time profiles in normal subjects after infusion of hetastarch 6070 500 ml. 34 In man, the urinary excretion is very rapid both during and immediately after infusion, with elimination rates of 2.19 and 2.34 g/h, respectively. :"':" This rate decreases with time to 1.40, 0.40, 0.15, and 0.08 g/h at 2 to 4-, 4 to 8-, 12 to 24-, and 24 to 48-hour urinary collection periods, respectively.…”

“…Biologic halflives of 67 hours to 240 days have been reported for hetastarch. 10,34,[42][43][44] While the short half-life was determined from inadequate data points, the long half-life (240 d) can be attributed to an unsuitable assay method010gy44 and use of a few points taken after long times when hetastarch levels were near and easily confused with background. In that the biologic half-life of hetastarch changes as a function of time, it is necessary to define the time period being studied.…”

What Is the Best Way to Fluid-Resuscitate a Patient with Sepsis?

“…The average terminal half-life is 17 days. Plasma volume expansion persists for at least 48 hours, 36 with 40% of the peak effect persisting after 24 hours. Hetastarch produces a significantly greater increase in plasma COP compared with an equal volume of 5% albumin.…”

Mass spectrometry of partially methylated alditol acetates derived from hydroxyethyl starch

“…Studies on the pharmacokinetics of hydroxyethyl starch in humans have been performed with faeces 6 and with urine 7 using trimethylsilyl (TMS) derivatives derived from HES. The methylation of carbohydrates and further derivatization to partially methylated alditol acetates (PMAAs) is a common method in sugar analysis 8 -12 to obtain unambiguous information regarding the position of linkages and to determine the extent of branching.…”