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

Abstract

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. In an open-label, uncontrolled, single-center study, 12 healthy male Japanese volunteers received single intravenous infusions of 500ml 6% HES 130/0.4 (Voluven 6%; Fresenius Kabi Deutschland, Bad Homburg, Germany) over 30min. Plasma concentration of 6% HES 130/0.4 was highest at end of infusion (5.53±0.55mg/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±0.16l/h, 1.12±0.26h, and 9.98±2.38h, respectively, and the volume of distribution was 4.76±0.64l. Mean area under the concentration-time curve was 26.7±3.75mg/mlh. 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±0.4g/dl at baseline to 13.8±0.4g/dl after the end of infusion. Adverse events in this study refer to changes of laboratory parameters and were assessed as not clinically relevant. Single administration of a 500ml 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 24h 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.