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


CONCLUSIONS
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.
Department of Anesthesiology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan. yamakage@sapmed.ac.jp
Michiaki
M
Yamakage
Frank
F
Bepperling
Manfred
M
Wargenau
Hideki
H
Miyao
D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004032:Diet; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D008297:Male; D015233:Models, Statistical; D010952:Plasma Substitutes / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D055815:Young Adult
D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes