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Pharmacokinetics of Hydroxyethyl Starch

 

作者: Cornelius Jungheinrich,   Thomas A Neff,  

 

期刊: Clinical Pharmacokinetics  (ADIS Available online 2005)
卷期: Volume 44, issue 7  

页码: 681-699

 

ISSN:0312-5963

 

年代: 2005

 

出版商: ADIS

 

关键词: Hetastarch, pharmacokinetics;Hetastarch, pharmacodynamics;Pentastarch, pharmacodynamics;Pentastarch, pharmacokinetics;Tetrastarch, pharmacokinetics;Tetrastarch, pharmacodynamics;Hydroxyethyl starches, pharmacodynamics;Hydroxyethyl starches, pharmacokineti

 

数据来源: ADIS

 

摘要:

Hydroxyethyl starch has recently become the subject of renewed interest because of the introduction of a new specification, hydroxyethyl starch 130/0.4, as well as the clinical availability of a solution using a previous hydroxyethyl starch type (hydroxyethyl starch 670/0.75) with a carrier other than 0.9% saline.Various types of hydroxyethyl starch show different pharmacokinetic behaviour. Since hydroxyethyl starch is a polydisperse solution acting as a colloid, pharmacodynamic action depends on the number of oncotically active molecules, not on the plasma concentration alone; therefore, solutions with a lowerin vivomolecular weight contain more molecules at similar plasma concentrations. On the other hand, high plasma concentrations as well as highin vivomolecular weight can affect blood coagulation, especially factor VIII and von Willebrand factor.Hydroxyethyl starch types with a molar substitution >0.4 accumulate in plasma after repetitive administration, most pronounced with hetastarch (hydroxyethyl starch 670/0.75). Correspondingly, tissue storage as measured by14C tracer studies  in  animals  showed  significantly  higher  values  for  hydroxyethyl starch 200/0.5 compared with hydroxyethyl starch 130/0.4 (about 4-fold at the latest timepoint  after  the  last  administration),  and  considerably  higher  values  for hetastarch compared with both hydroxyethyl starch 130/0.4 and 200/0.5.Hydroxyethyl starch 130/0.4 does not accumulate in plasma after single- and multiple-dose administration in contrast to all other available hydroxyethyl starch specifications. Plasma clearance of hydroxyethyl starch 130/0.4 is at least 20-fold higher than that for hetastarch, and considerably higher than for pentastarch. In patients with renal insufficiency, pharmacokinetic data are only available for hydroxyethyl starch 130/0.4. Cumulative urinary excretion, even in the presence of severe non-anuric renal failure, is higher for hydroxyethyl starch 130/0.4 than values published for older hydroxyethyl starch specifications. Hydroxyethyl starch 130/0.4 may be given to patients with severe renal impairment as long as urine flow is preserved.The pharmacodynamics with respect to the volume effect does not directly mirror pharmacokinetics in the case of hydroxyethyl starch solutions. Equivalent volume efficacy has been proven for hydroxyethyl starch 130/0.4 compared with 200/0.5. Prolonged persistence of hydroxyethyl starch in plasma and tissues can be avoided by using rapidly metabolisable hydroxyethyl starch types with molar substitution <0.5. Influence on coagulation is minimal with hydroxyethyl starch 130/0.4, and no adverse effects on kidney function have been observed even with large repetitive doses when used according to the product information.

 

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