HES 130/0.42 shows less alteration of pharmacokinetics than HES 200/0.5 when dosed repeatedly
1 Department of Anaesthesiology and Intensive Care Medicine, Friedrich Schiller University, Jena, Germany
2 Department of Experimental Anaesthesiology, Johann Wolfgang Goethe University, Frankfurt/Main, Germany
3 Medical Department, B. Braun Melsungen AG, Melsungen, Germany
4 Department of Biometrics and Statistics, Georg-August-University, Goettingen, Germany
* Corresponding author: Department of Anaesthesiology and Intensive Care Medicine, Friedrich Schiller University, Erlanger Allee 101, 07740 Jena, Germany
Background: Hydroxyethyl starches (HES) accumulate in the circulation when administered repeatedly. Accumulation is thought to be partly responsible for undesirable effects (tissue storage, blood coagulation impairment, and itching). HES 130/0.42 with low molecular weight and a low level of substitution has recently been developed in order to reduce those risks.
Methods: In healthy volunteers, the pharmacokinetics of HES 130/0.42/6:1 were investigated using a crossover design with HES 200/0.5 serving as control. Fifty grams of either HES were administered in 4 h day–1 for a period of five consecutive days. HES serum concentrations were used for computation of pharmacokinetic coefficients. Change between the first and fifth infusion in the area under the concentration curve (AUC) served as the primary measurement.
Results: Although the circulation was freed from the load with HES 130/0.42 within 20 h after end of the previous infusion, the amount of HES 200/0.5 increased continuously from one administration to the other. AUC and elimination half-life (t1/2) were significantly lower with HES 130/0.42. AUC and t1/2 of HES 200/0.5 showed an increase between the first and the fifth administration whereas only a minimal shift was present with HES 130/0.42. Haemodilution via HES 200/0.5 did not change over time.
Conclusions: Repeated administration of HES 130/0.42 shows no accumulation and fewer tendencies to time-dependent changes in pharmacokinetic parameters than HES 200/0.5. The improved reproducibility may improve drug safety, particularly as the accumulation of residual starch with HES 200/0.5 does not contribute to the colloid's volume effect, but may rather increase the risk of undesired reactions.
Keywords: hydroxyethyl starch, low molecular weight, low substituted; pharmacokinetics, repeated dose; pharmacodynamics; volunteers
Declaration of interest. Dr Burmeister and Dr Boll are employees of B. Braun AG Melsungen. Prof. Förster, Prof. Hilgers, Prof. Marx, Dr Asskali, and Dr Lehmann have done paid consultation for B. Braun AG Melsungen. The Department of Anaesthesiology and Intensive Care Medicine of the University of Jena has done other research projects in collaboration with B. Braun Melsungen AG and has thereby received other funding in the past. The Department of Anaesthesiology and Intensive Care Medicine of the University of Jena has also received educational funds from competitor companies. The Department of Experimental Anaesthesiology of the University of Frankfurt/Main has done other research projects in collaboration with B. Braun Melsungen AG and has thereby received other funding in the past. The Department of Medical Statistics of the University of Goettingen has done research projects in collaboration with B. Braun Melsungen AG and has thereby received funding. The Department of Medical Statistics of the University of Goettingen has also received funds from competitor companies.