HES 130/0.42 shows less alteration of pharmacokinetics than HES 200/0.5 when dosed repeatedly.
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.
Lehmann
G B
GB
Department of Anaesthesiology and Intensive Care Medicine, Friedrich Schiller University, Jena, Germany.
Asskali
F
F
Boll
M
M
Burmeister
M A
MA
Marx
G
G
Hilgers
R
R
Förster
H
H
D000328:Adult; D001809:Blood Viscosity; D004812:Epidemiologic Methods; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000009:adverse effects / Q000097:blood* / Q000737:chemistry; D008297:Male; D008970:Molecular Weight; D009997:Osmotic Pressure; D010952:Plasma Substitutes / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D000516:alpha-Amylases / Q000097:blood
D006454:Hemoglobins; D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes; D000516:alpha-Amylases