Journal of Anesthesia

, Volume 26, Issue 6, pp 851–857 | Cite as

Pharmacokinetics and safety of 6 % hydroxyethyl starch 130/0.4 in healthy male volunteers of Japanese ethnicity after single infusion of 500 ml solution

  • Michiaki Yamakage
  • Frank Bepperling
  • Manfred Wargenau
  • Hideki Miyao
Original Article

Abstract

Purpose

This phase I study was performed in volunteers of Japanese ethnicity to compare pharmacokinetic data after infusion of 6 % hydroxyethyl starch (HES) 130/0.4 with historical data of Caucasians.

Methods

In an open-label, uncontrolled, single-center study, 12 healthy male Japanese volunteers received single intravenous infusions of 500 ml 6 % HES 130/0.4 (Voluven 6 %; Fresenius Kabi Deutschland, Bad Homburg, Germany) over 30 min.

Results

Plasma concentration of 6 % HES 130/0.4 was highest at end of infusion (5.53 ± 0.55 mg/ml) and decreased following a biphasic manner. Total plasma clearance and rapid and slow elimination half-lives obtained by a two-compartment model were 1.14 ± 0.16 l/h, 1.12 ± 0.26 h, and 9.98 ± 2.38 h, respectively, and the volume of distribution was 4.76 ± 0.64 l. Mean area under the concentration–time curve was 26.7 ± 3.75 mg/ml h. The total amount of HES excreted into urine was 59.4 % of the applied dose. Hemodilution was observed in all 12 subjects as indicated by a decrease of hemoglobin from 15.5 ± 0.4 g/dl at baseline to 13.8 ± 0.4 g/dl after the end of infusion. Adverse events in this study refer to changes of laboratory parameters and were assessed as not clinically relevant.

Conclusion

Single administration of a 500 ml solution of 6 % HES 130/0.4 was confirmed to be safe and tolerable in healthy male Japanese subjects. A rapid renal excretion was observed within 24 h after drug administration, accounting for 96 % of the total amount excreted. A comparison with pharmacokinetic data derived from Caucasians did not reveal significant differences to Japanese and confirmed the good tolerability in both ethnic groups.

Keywords

Hydroxyethyl starch 6 % HES 130/0.4 Pharmacokinetics Safety Japanese healthy male volunteers 

Notes

Acknowledgments

We thank Dr. Fukase/Kouryokai CPC Clinic Kagoshima for conducting the clinical study.

Conflict of interest

Voluven® is a product of Fresenius Kabi. Dr. Bepperling is an employee of this company, and Dr. Miyao is a Medical Consultant to this company.

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Copyright information

© Japanese Society of Anesthesiologists 2012

Authors and Affiliations

  • Michiaki Yamakage
    • 1
  • Frank Bepperling
    • 2
  • Manfred Wargenau
    • 3
  • Hideki Miyao
    • 4
  1. 1.Department of AnesthesiologySapporo Medical University School of MedicineSapporoJapan
  2. 2.Fresenius Kabi DeutschlandBad HomburgGermany
  3. 3.M.A.R.C.O. Institute for Clinical Research and StatisticsDüsseldorfGermany
  4. 4.Department of Anesthesiology, Saitama Medical CenterSaitama Medical UniversityKawagoeJapan

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