Clinical Drug Investigation

, Volume 16, Issue 2, pp 151–160

Pharmacokinetics and Tolerability of a New Hydroxyethyl Starch (HES) Specification [HES (130/0.4] after Single-Dose Infusion of 6% or 10% Solutions in Healthy Volunteers

  • Josef Waitzinger
  • Frank Bepperling
  • Günther Pabst
  • Jens Opitz
  • Margarete Müller
  • Jean François Baron


Objective: To investigate the pharmacokinetic profile and tolerability of a single-dose infusion of the new hydroxyethyl starch (HES) specification, HES (130/0.4), 6% and 10% solutions in healthy volunteers.

Study Design: In an open, randomised, single-dose, parallel-group study, 12 healthy volunteers (in each group) received intravenous infusions of 500ml of a new HES specification [HES (130/0.4)] of either 6% or 10% solution within 30 minutes.

Results: Plasma elimination initially occurred with an α half-life of approximately 0.5 to 0.75 hour. A half-life of approximately 12 hours was reported for the terminal phase. Between 60 to 70% of the total plasma elimination was due to renal excretion. The total plasma clearances of 31.4 ml/min and 26.0 ml/min for the 6 and 10% solutions, respectively, were higher than those reported for other HES specifications. The volume of distribution in the central compartment was approximately 5.9L, which roughly corresponded to the blood volume. Single doses of 6% and 10% HES (130/0.4) were well tolerated.

Conclusion: The new HES specification demonstrated favourable pharmacokinetic properties compared with other HES specifications of medium or high molecular weight. No clinically relevant plasma accumulation and related undesired effects on haemostasis are expected to occur under multiple-dose conditions.


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  1. 1.
    Jung F, Koscielny J, Mrowietz C, et al. Elimination kinetics of different hydroxethyl starches and effects on blood fluidity. Clin Hemorheol 1994; 14: 189–202Google Scholar
  2. 2.
    Rackow EC, Falk JL, Fein IA, et al. Fluid resuscitation in circulatory shock: A comparison of the cardiorespiratory effects of albumin, hetastarch, and saline solutions in patients with hypovolemic and septic shock. Crit Care Med 1983; 11(11): 839–50PubMedCrossRefGoogle Scholar
  3. 3.
    Moggio RA, Reha CC, Somberg ED, et al. Hemodynamic comparison of albumin and hydroxyethyl starch on postoperative surgery patients. Crit Care Med 1983; 11(12): 943–5PubMedCrossRefGoogle Scholar
  4. 4.
    Vogt NH, Bothner U, Lerch G, et al. Large-dose administration of 6% hydroxyethyl starch 200/0.5 for total hip arthroplasty: plasma homeostasis, hemostasis, and renal function compared to use of 5% human albumin. Anesth Analg 1996; 83: 262–8PubMedGoogle Scholar
  5. 5.
    Boldt J, Knothe C, Schindler E, et al. Volume replacement with hydroxyethyl starch solution in children. Br J Anaesth 1993; 70: 661–5PubMedCrossRefGoogle Scholar
  6. 6.
    Sommermeyer K, Czech F, Schmidt M, et al. Klinisch verwendete Hydroxy-ethylstärke: physikalisch-chemische Charaktersisierung. Krankenhauspharmazie 1989; 8: 271Google Scholar
  7. 7.
    Ferber HP, Nitsch E, Förster H. Studies on Hydroxyethyl Starch: Pt II: Changes of the molecular weight distribution for hydroxyethyl starch types 450/0.7, 450/0.5, 450/0.3, 300/0.4, 200/0.7, 200/0.5, 200/0.3 and 200/0.1 after infusion in serum and urine of volunteers. Arzneimittel Forschung 1985; 35(3): 615–22PubMedGoogle Scholar
  8. 8.
    Treib J, Haass A, Pindur G, et al. HES 200/0.5 is not HES 200/0.5. Influence of the C2/C6 hydroxyethylation ratio of hydroxyethyl starch (HES) on hemorheology, coagulation and elimination kinetics. Thromb Haemost 1995; 74(6): 1452–6PubMedGoogle Scholar
  9. 9.
    Weidler B, von Bormann B, Sommermeyer K, et al. Pharmakokinetische Merkmale als Kriterien für den klinischen Einsatz von Hydroxyethylstärke. Arzneimittel Forschung 1991; 41(5): 494–8PubMedGoogle Scholar
  10. 10.
    Metze D, Reimann S, Szepefalusi Z, et al. Persistent pruritus after hydroxyethyl starch infusion therapy: a result of long-term storage in cutaneous nerves. Br J Dermatol 1997 Apr; 136(4): 553–9PubMedCrossRefGoogle Scholar
  11. 11.
    Yacobi A, Stoll RG, Sum CY, et al. Pharmacokinetics of hydoxyethyl starch in normal subjects. J Clin Pharmacol 1982; 22: 206–12PubMedGoogle Scholar
  12. 12.
    Quon CY. Clinical pharmacokinetics and pharmacodynamics of colloidal plasma volume expanders. J Cardiothorac Anesth 1988; 6: 13–23CrossRefGoogle Scholar
  13. 13.
    Degremont AC, Ismail M, Arthaud M, et al. Mechanisms of postoperative prolonged plasma volume expansion with low molecular weight hydroxyethyl starch (HES 200/0.62; 6%). Intensive Care Med 1995; 21: 577–83PubMedCrossRefGoogle Scholar
  14. 14.
    Mishler J, Duerr HK. Macroamylasemia induced hydroxyethyl starch confirmation by gel filtration analysis of serum and urine. J Clin Pathol 1980; 74(4): 387–91Google Scholar
  15. 15.
    Koehler H, Kirch W, Weihrauch TR, et al. Macroamylasaemia after treatment with hydrox. Eur J Clin Invest 1977; 7: 205–11CrossRefGoogle Scholar
  16. 16.
    Koehler H, Zschiedrich H, Linfante A, et al. Die Elimination von Hydoxyaethylstaerke 200/0.5, Dextran 40 und Oxypolygelatine. Klin Wochenschr 1982; 60: 293–301CrossRefGoogle Scholar
  17. 17.
    Baron JF. Low molecular weight hydroxyethyl starches. In Baron JF, editor. Plasma volume expansion. Paris: Arnette Backwell, 1992: 121–32Google Scholar
  18. 18.
    Laxenaire MC, Charpentier C, Feldman L, et al. Anaphylactoid reactions to colloid plasma substitutes: frequency, risk factors, mechanisms. A French prospective multicentre inquiry [in French]. Ann Fr Anesth Rèanim 1994; 13: 301–10PubMedCrossRefGoogle Scholar
  19. 19.
    Kreimeier U, Christ F, Kraft D, et al. Anaphylaxis due to hydroxyethyl-starch-reactive antibodies. Lancet 1995; 346: 40–50CrossRefGoogle Scholar
  20. 20.
    Cittenova ML, Leblanc I, Legendre Ch, et al. Effect of hydroxyethyl starch in brain-dead kidney donors on renal function in kidney-transplant recipients. Lancet 1996; 348: 1620–2CrossRefGoogle Scholar
  21. 21.
    Treib J, Haass A, Pindur G. Coagulation disorders caused by hydroxyethyl starch. Thromb Haemost 1997; 78: 974–83PubMedGoogle Scholar
  22. 22.
    Strauss RG. Volume replacement and coagulation: a comparative review. J Cardiothorac Vasc Anesth 1988; 6Suppl. 2: 24–32Google Scholar
  23. 23.
    Claes Y, Van Hemelrijck J, Van Gerven M, et al. Influence of hydroxyethyl starch on coagulation in patients during the perioperative period. Anesth Analg 1992; 75: 24–30PubMedCrossRefGoogle Scholar
  24. 24.
    Cope JT, Banks D, Mauney MC, et al. Intraoperative hetastarch infusion impairs hemostasis after cardiac operations. Ann Thorac Surg 1997; 63: 78–83PubMedCrossRefGoogle Scholar
  25. 25.
    Strauss RG, Stansfield C, Henriksen A, et al. Pentastarch may cause fewer effects on coagulation than hetastarch. Transfusion 1988; 28: 257–60PubMedCrossRefGoogle Scholar
  26. 26.
    Gröchenig E, Albegger K, Dieterich HJ, et al. Hydroxyethyl starch-related pruritus: a prospective multicentre investigation of 544 patients. Perfusion 1998; 11: 62–9Google Scholar

Copyright information

© Adis International Limited 1998

Authors and Affiliations

  • Josef Waitzinger
    • 1
  • Frank Bepperling
    • 2
  • Günther Pabst
    • 1
  • Jens Opitz
    • 2
  • Margarete Müller
    • 1
  • Jean François Baron
    • 3
  1. 1.L.A.B. GmbH & CoNeu-UlmGermany
  2. 2.FRESENIUS AG Pharmaceuticals DivisionBad HomburgGermany
  3. 3.Départment d’Anesthésie-RéanimationHôpital BroussaisParisFrance

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