Hydroxyethyl Starch (HES) [130/0.4], a New HES Specification
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ORIGINAL RESEARCH ARTICLE
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Hydroxyethyl Starch (HES) [130/0.4], a New HES Specification Pharmacokinetics and Safety after Multiple Infusions of 10% Solution in Healthy Volunteers ¨ Josef Waitzinger,1 Frank Bepperling,2 Gunther Pabst1 and Jens Opitz2 1 2
AAI Deutschland GmbH & Co KG, Neu-Ulm, Germany FRESENIUS Kabi AG Deutschland GmbH, Bad Homburg, Germany
Abstract
Objective: To investigate the pharmacokinetics and safety of a daily infusion of 500mL of hydroxyethyl starch (HES) [130/0.4] 10% solution on 10 consecutive days. Study design and participants: An open, one-way, multiple-dose study was performed in 12 healthy male volunteers. Daily infusions over 30 minutes of 500mL of HES (130/0.4) 10% solution were performed on 10 consecutive days. Plasma and urine HES concentrations were determined repeatedly during the study until 72 hours after the last infusion. Results: Maximum plasma HES concentrations, assessed with geometric means of 7.7 and 7.4 mg/mL, respectively, as well as the time courses of the plasma concentrations were similar on days 1 and 10 of treatment. Plasma HES concentrations 24 hours after the last infusion were 0.48 mg/mL (mean). Total plasma clearance was calculated as 23.7 and 21.8 mL/min on days 1 and 10, respectively. Urinary recoveries of 69% on day 1 and of 70% on day 10 were in good agreement. Conclusion: The results clearly demonstrated that there is no relevant accumulation in plasma after repetitive infusion of the medium-molecular weight HES (130/0.4) solution, which exhibits a high renal excretion rate over 10 days. Local as well as systemic tolerability of 10 repeated doses was good.
Hydroxyethyl starch (HES) infusion solutions have long been used for volume replacement therapy worldwide. Commercially available specifications vary greatly in molecular weight and molar substitution, reflecting different pharmacological profiles.[1] The first registered HES solution was a
high-molecular weight specification HES (HES 450/0.7), which is still available in the US. Some years later HES 70/0.5 was developed in Japan. In Europe, HES solutions based on a medium-molecular weight specification (e.g. HES 200/0.5) are predominantly used. Efficacy, safety and tolerability of
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these specifications were evaluated in several clinical studies.[2-4] Clinical limitations in the use of HES are mainly related to interactions with the coagulation system, although bleeding complications are predominantly described with high-substituted HES.[1] Consequently, depending on dose recommendations, either the maximum dose or clinical practice limit the administration of HES. This is disadvantageous in the treatment of patients with high blood loss. The aim of the development of HES (130/0.4) was to further improve the pharmacokinetic and molecular distribution profile of HES, which should lead to a decrease in plasma accumulation and associated coagulation impairment, and to lower tissue storage of HES after repeated administrati
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