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01.05.2003 | Original Research Article

Hydroxyethyl Starch (HES) [130/0.4], a New HES Specification

Pharmacokinetics and Safety after Multiple Infusions of 10% Solution in Healthy Volunteers

verfasst von: Dr Josef Waitzinger, Frank Bepperling, Günther Pabst, Jens Opitz

Erschienen in: Drugs in R&D | Ausgabe 3/2003

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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.

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Treib J, Baron J-F, Grauer MT, et al. An international view of hydroxyethyl starch. Intensive Care Med 1999; 25: 258–68PubMedCrossRef

Gan TJ, Bennett-Guerrero E, Phillips-Bute B, et al. Hextend, a physiologically balanced plasma expander for large volume use in major surgery: a randomized phase III clinical trial. Anesth Analg 1999; 92: 1402–7

Fukusaki M, Nakamura T, Fukushima H, et al. Splanchnic perfusion during controlled hypotension with haemodilution under isoflurane anaesthesia in elderly patients. Eur J Anaesthesiol 1999; 16: 519–525PubMed

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: 262–8PubMed

Waitzinger J, Bepperling F, Pabst G, et al. Pharmacokinetics and tolerability of a new hydroxyethyl starch (HES) specification [HES (130/0.4)] after single-dose infusion of 6% and 10% solutions in healthy volunteers. Clin Drug Invest 1998; 16: 151–60CrossRef

Committee for Proprietary Medicinal Products (CPMP). Note for guidance on the investigation of bioavailability and bioequivalence (CPMP/EWP/QWP/1401/98)

Friedrich G, Ott E. Prospektive randomisierte Studie zum Wirkungsvergleich zwischen 10% HES 200/0.5 and 6% HES 200/0.5 bei Hörsturzpatienten. Laryngol Rhinol Otol 1991; 70: 670–4CrossRef

Mishler JM, Beez M. Die mathematische Beschreibung der intravasalen Ausscheidung von HAES nach der wiederholten Infusionen beim Menschen. Infusionsther Klin Ernahr 1979; 6 (2): 3–6

Asskali F, Föorster H. Zur Kumulation unterschiedlich substituierter Hydroxyethylstärke (HES) nach repetitiver Infusion bei gesunden Versuchsprobanden. Anasthesiol Intensivmed Notfallmed Schmerzther 1999; 34: 537–41PubMedCrossRef

10.

Lehmann G, Asskali F, Förster H. Pharmacokinetics of hydrox-yethyl starch (70/0.5) following repeated infusions. Transfus Med Hemother 2003; 30: 72–7CrossRef

11.

Koeltringer P, Pfeiffer P, Lind P, et al. Haemodilution mit mittelmolekularer Hydroxyaethylstaerke — 6% HES 200/0,6-0,66 - bei Patienten mit peripherer arterieller Verschluß-krankheit. Österr Krankenhauspharmazie 1989; 2: 7–12

12.

Treib J, Haas A, Pindur G, et al. Influence of intravascular molecular weight of hydroxyethyl starch on platelets. Eur J Haematol 1996; 56: 168–72PubMedCrossRef

13.

Kroemer H, Haass A, Müller K, et al. Haemodilution therapy in ischemic stroke: plasma concentrations and plasma viscosity during long-term infusion of Dextran 40 or Hydroxyethyl starch 200/0.5. Eur J Clin Pharmacol 1987; 31: 705–10PubMedCrossRef

14.

Jung F, Koscielny J, Mrowietz C, et al. Elimination kinetics of different hydroxyethyl starches and effects on blood fluidity. Clin Hemorheol 1993; 14: 189–202

15.

Metcalf W, Papadopoulos A, Tufaro R, et al. Clinical physiology study of hydroxyethyl starch. Surg Gynecol Obstet 1970; 131 (2): 255–67PubMed

16.

Boldt J, Mueller M, Menges T, et al. Influence of different therapy regimens on regulators of the circulation in the critically ill. Br J Anesth 1996; 77: 480–7CrossRef

17.

Aichner FT, Fazekas F, Brainin M, et al. Hypervolemic hemodilution in acute ischemic stroke: The Multicenter Austrian Hemodilution Stroke Trial (MAHST). Stroke 1998; 29: 743–9PubMedCrossRef

18.

Trumble ER, Muizelaar JP, Myseros JS, et al. Coagulopathy with the use of hetastarch in the treatment of vasospasm. J Neurosurg 1995; 82: 44–7PubMedCrossRef

19.

Strauss RG, Pennell BJ, Stump DC. A randomised, blinded trial comparing the hemostatic effects of pentastarch versus hetastarch. Transfusion 2002; 42: 27–36PubMedCrossRef

20.

Huet RCG, Siemons AW, Baus D, et al. A novel hydroxyethyl starch (Voluven®) for effective perioperative plasma volume substitution in cardiac surgery. Can J Anesth 2000; 47: 1207–15CrossRef

21.

Langeron O, Doelberg M, Eng-Than A, et al. Voluven®, a lower substituted novel hydroxyethyl starch (HES 130/0.4), causes fewer effects on coagulation in major orthopedic surgery than HES 200/0.5. Anesth Analg 2001; 92: 855–62PubMedCrossRef

22.

Jungheinrich C, Scharpf R, Wargenau M, et al. The pharmaco kinetics and tolerability of an intravenous infusion of the new hydroxyethyl starch 130/0.4 (6%, 500 ml) in mild-to-severe renal impairment. Anesth Analg 2002; 95: 544–51PubMed

23.

Koehler H, Kirch W, Weihrauch TR, et al. Macroamylasaemia after treatment with hydroxyethyl starch. Eur J Clin Invest 1977; 7: 205–11CrossRef

24.

Rosenzweig P, Miget N, Brohier S. Transaminase elevation on placebo during phase I trials: prevalence and significance. Br J Clin Pharmacol 1999; 48: 19–23PubMedCrossRef

25.

Rudolf J. Hydroxyethyl starch for hypervolemic hemodilution in patients with acute ischemic stroke: a randomized, placebocontrolled phase II safety study. Cerebrovasc Dis 2002; 14: 33–41PubMedCrossRef

26.

Neff TA, Doelberg M, Jungheinrich C, et al. Repetitive largedose infusion of the novel hydroxyethyl starch 130/0.4 in patients with severe head trauma. Anesth Analg 2003; 96: 1453–9PubMedCrossRef

Titel: Hydroxyethyl Starch (HES) [130/0.4], a New HES Specification
Pharmacokinetics and Safety after Multiple Infusions of 10% Solution in Healthy Volunteers
verfasst von: Dr Josef Waitzinger
Frank Bepperling
Günther Pabst
Jens Opitz
Publikationsdatum: 01.05.2003
Verlag: Springer International Publishing
Erschienen in: Drugs in R&D / Ausgabe 3/2003
Print ISSN: 1174-5886
Elektronische ISSN: 1179-6901
DOI: https://doi.org/10.2165/00126839-200304030-00002

Springer Medizin

Abstract

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