Novel starches: single-dose pharmacokinetics and effects on blood coagulation.
BACKGROUND
Carboxymethyl starch (CMS) and carboxymethylated hydroxyethyl starch (CM-HES) might offer advantages over hydroxyethyl starch (HES) with regard to their volume expansion effect and their pharmacokinetic characteristics. The goal of the current study was to determine the pharmacokinetics of CMS and CM-HES and to investigate their influence on blood coagulation in comparison with the standard low-molecular, low-substituted HES (130/0.42) used in Europe.


METHODS
The study was conducted as a randomized, blinded, parallel three-group study in 30 pigs. Twenty ml/kg of 6% HES (control), 6% CMS, or 6% CM-HES was infused as a single dose, and serial blood sampling was performed over 20 h to measure plasma concentration and molecular weight and to assess blood coagulation. Concentration-effect relations were assessed by pharmacokinetic-pharmacodynamic analysis.


RESULTS
CMS and CM-HES showed significantly higher plasma concentrations and molecular weights over 20 h (P for both<0.001) with smaller volumes of distribution and longer elimination rates during the terminal phase (P for both<0.01) when compared with HES. CMS and CM-HES impaired whole blood coagulation more than HES as assessed by Thrombelastograph analysis (Haemoscope Corporation, Niles, IL). However, similar effects of all three starch preparations on blood coagulation were found when related to the plasma concentrations in mass units.


CONCLUSIONS
Carboxymethylation of starch results in an increased intravascular persistence and a slower fragmentation compared with HES. The greater impairment of blood coagulation by CMS and CM-HES seems to be caused by the higher plasma concentrations.
Madjdpour
Caveh
C
Department of Anesthesiology, Division of Clinical Pharmacology and Toxicology, University Hospital Lausanne, Switzerland.
Thyes
Caroline
C
Buclin
Thierry
T
Frascarolo
Philippe
P
von Roten
Inès
I
Fisch
Andreas
A
Burmeister
Marc
M
Bombeli
Thomas
T
Spahn
Donat R
DR
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D001802:Blood Substitutes / Q000493:pharmacokinetics*; D003102:Colloids; D006438:Hemodilution; D006454:Hemoglobins / Q000032:analysis; D006895:Hydroxyethyl Starch Derivatives / Q000493:pharmacokinetics* / Q000494:pharmacology; D009997:Osmotic Pressure; D013213:Starch / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D013552:Swine
D001802:Blood Substitutes; D003102:Colloids; D006454:Hemoglobins; D006895:Hydroxyethyl Starch Derivatives; D013213:Starch; C034848:carboxymethyl starch