• Drugs in R&D · Jan 2003

    Comparative Study

    Tissue storage of 14C-labelled hydroxyethyl starch (HES) 130/0.4 and HES 200/0.5 after repeated intravenous administration to rats.

    • Jost Leuschner, Jens Opitz, Andreas Winkler, Roland Scharpf, and Frank Bepperling.
    • LPT Laboratory of Pharmacology and Toxicology, Hamburg, Germany.
    • Drugs R D. 2003 Jan 1;4(6):331-8.

    ObjectiveTo investigate the effect of the molar substitution of hydroxyethyl starch (HES) solutions on tissue and organ storage in rats after repeated administration.Study DesignA controlled, multiple-dose study was performed in 48 rats. Daily bolus injections of 0.7 g/kg of 10% HES 130/0.4 or 10% HES 200/0.5 were administered on 18 consecutive days. In order to examine quantitatively the distribution and excretion of both preparations on HES tissue storage, radiolabelled HES was measured 3, 10, 24 and 52 days after the last administration. Tissue storage was expressed as percentage radioactivity of total administered HES dose in the total body, carcass, liver, kidney, spleen, lymph nodes, plasma and urine.Results52 days after the last administration the remaining radioactivity of labelled HES 200/0.5 was nearly 4-fold higher compared with HES 130/0.4 in the total body (2.45% vs 0.65% of the total administered dose). This difference in tissue storage was statistically significant (p < or = 0.01). A comparable difference was observed for the liver and carcass.ConclusionTissue storage after repeated administration of an HES solution with a low molar substitution (0.4) was significantly lower in the total body as well as in the liver and carcass compared with an HES solution with a medium molar substitution (0.5). However, the potential clinical consequences of these present findings have not yet been determined.

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