title: Novel starches: single-dose pharmacokinetics and effects on blood coagulation.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Division of Clinical Pharmacology and Toxicology, University Hospital Lausanne, Switzerland.
authors.forename: Caveh
authors.initials: C
authors.lastname: Madjdpour
authors.forename: Caroline
authors.initials: C
authors.lastname: Thyes
authors.forename: Thierry
authors.initials: T
authors.lastname: Buclin
authors.forename: Philippe
authors.initials: P
authors.lastname: Frascarolo
authors.forename: Inès
authors.initials: I
authors.lastname: von Roten
authors.forename: Andreas
authors.initials: A
authors.lastname: Fisch
authors.forename: Marc
authors.initials: M
authors.lastname: Burmeister
authors.forename: Thomas
authors.initials: T
authors.lastname: Bombeli
authors.forename: Donat R
authors.initials: DR
authors.lastname: Spahn
mesh_terms: 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
chemical_list: D001802:Blood Substitutes; D003102:Colloids; D006454:Hemoglobins; D006895:Hydroxyethyl Starch Derivatives; D013213:Starch; C034848:carboxymethyl starch