Bioequivalence Comparison between Hydroxyethyl??Starch??130/0.42/6???:???1 and??Hydroxyethyl Starch??130/0.4/9???:???1

Abstract

The aim of this study was to investigate whether a recently developed low molecular, low substituted hydroxyethyl starch (HES 130/0.42/6 : 1), altered in molar substitution and C2/C6 ratio, is bioequivalent to the former standard HES preparation (130/0.4/9 : 1). The two HES solutions were infused (60g as a single dose within 30 minutes) in healthy volunteers using a randomised, crossover design. HES serum concentrations were used for computation of pharmacokinetic parameters; area under the concentration-time curve from infusion start until 24 hours thereafter (AUC(24)) and maximum serum concentration (C(max)) were the primary criteria. Haemodilution, colloid osmotic pressure and plasma viscosity were measured as secondary criteria. Pentastarch (HES 200/0.5/5:1) was investigated in the same volunteers and manner during a subsequent period. Using non-compartmental analysis, significant differences were found for AUC(24) (45.97 +/- 8.97 mg . h/mL vs 58.32 +/- 9.23 mg . h/mL; HES 130/0.42/6 : 1 vs HES 130/0.4/9 : 1) and total apparent clearance (CL; 1.14 +/- 0.4 L/h vs 0.81 +/- 0.34 L/h). C(max) and elimination half-life (t(1/2)) were similar, while the AUC(24), t(1/2) and CL of pentastarch were significantly different from those of low substituted HES solutions. Being equivalent with pentastarch and HES 130/0.4/9 : 1 in terms of colloid osmotic and haemodilution effect, HES 130/0.42/6 : 1 shows the fastest clearance from the circulation.