Madjdpour Caveh, Thyes Caroline, Buclin Thierry, Frascarolo Philippe, von Roten Inès, Fisch Andreas, Burmeister Marc, Bombeli Thomas, Spahn Donat R
Department of Anesthesiology, Division of Clinical Pharmacology and Toxicology, University Hospital Lausanne, Switzerland.
Anesthesiology. 2007 Jan;106(1):132-43. doi: 10.1097/00000542-200701000-00022.
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.
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.
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.
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.
羧甲基淀粉（CMS）和羧甲基化羟乙基淀粉（CM-HES）在扩容效果和药代动力学特征方面可能优于羟乙基淀粉（HES）。本研究的目的是确定CMS和CM-HES的药代动力学，并与欧洲使用的标准低分子、低取代度HES（130/0.42）相比，研究它们对血液凝固的影响。
本研究以随机、盲法、平行三组研究的方式在30头猪身上进行。以单剂量输注20ml/kg的6%HES（对照组）、6%CMS或6%CM-HES，并在20小时内进行系列采血，以测量血浆浓度和分子量，并评估血液凝固情况。通过药代动力学-药效学分析评估浓度-效应关系。
与HES相比，CMS和CM-HES在20小时内血浆浓度和分子量显著更高（两者P均<0.001），分布容积更小，终末相消除率更长（两者P均<0.01）。通过血栓弹力图分析（美国伊利诺伊州奈尔斯市血液观察仪器公司）评估，CMS和CM-HES对全血凝固的损害比HES更大。然而，当以质量单位的血浆浓度为参照时，发现三种淀粉制剂对血液凝固的影响相似。
与HES相比，淀粉的羧甲基化导致血管内持久性增加，碎片化减慢。CMS和CM-HES对血液凝固的更大损害似乎是由更高的血浆浓度引起的。
