Hydroxyethyl starch (HES) [130/0.4], a new HES specification: pharmacokinetics and safety after multiple infusions of 10% solution in healthy volunteers.
OBJECTIVE
To investigate the pharmacokinetics and safety of a daily infusion of 500 mL of hydroxyethyl starch (HES) [130/0.4] 10% solution on 10 consecutive days.


METHODS
An open, one-way, multiple-dose study was performed in 12 healthy male volunteers. Daily infusions over 30 minutes of 500 mL 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.


CONCLUSIONS
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.
Waitzinger
Josef
J
AAI Deutschland GmbH & Co KG, Neu-Ulm, Germany. Josef.Waitzinger@aai.de
Bepperling
Frank
F
Pabst
Günther
G
Opitz
Jens
J
D000328:Adult; D019540:Area Under Curve; D006207:Half-Life; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D008297:Male; D008970:Molecular Weight; D010952:Plasma Substitutes / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*
D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes