Plasma thrombin neutralization assay: pharmacokinetic applications.

Details

Serval ID
serval:BIB_0815FE106026
Type
Article: article from journal or magazin.
Collection
Publications
Title
Plasma thrombin neutralization assay: pharmacokinetic applications.
Journal
Seminars In Thrombosis and Hemostasis
Author(s)
Iorio A., Alatri A., Mazzolai L., Agnelli G.
ISSN
0094-6176 (Print)
ISSN-L
0094-6176
Publication state
Published
Issued date
1994
Volume
20
Number
3
Pages
266-273
Language
english
Notes
Publication types: Clinical Trial ; Journal Article ; Randomized Controlled Trial
Publication Status: ppublish
Abstract
UFH and its derivatives, LMWHs, are effective and safe in the prevention and treatment of DVT. The mechanism for this effectiveness has been difficult to explain, given that the anti-IIa activity of LMWHs is important for their antithrombotic activity and the reported half-life of the anti-IIa activity of LMWHs is very short. The standard chromogenic anti-IIa assay is performed in an artificial system consisting of highly diluted plasma to which antithrombin III is added. It is possible, therefore, that the apparently short half-life of the anti-IIa activity is dependent on the limitations of the anti-IIa assay, commonly used in the pharmacokinetic studies. We have developed an anti-IIa assay that is more sensitive than the standard one. Our assay is based on the ability of UFH or LMWHs to catalyze the formation of TAT complexes. PTNA was able to detect in vitro the anti-IIa activity produced by 0.01 anti-Xa IU/mL of UFH or 0.05 anti-Xa IU/mL of LMWHs. Ex vivo, it was able to describe the time course of plasma anti-IIa activity of very low doses of UFH (intravenous or subcutaneous) or LMWHs. To characterize better the role of the anti-IIa activity of LMWHs, the pharmacokinetic properties of two of these agents have been evaluated in humans, assessing the anti-IIa activity by PTNA. Fraxiparine, 7500 and 10,000 ICU, and Enoxaparine, 20 and 40 mg, were administered subcutaneously to six healthy volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)
Keywords
Adult, Blood Coagulation Tests, Chromogenic Compounds, Drug Evaluation, Female, Heparin/pharmacokinetics, Heparin/pharmacology, Heparin, Low-Molecular-Weight/pharmacokinetics, Heparin, Low-Molecular-Weight/pharmacology, Humans, Male, Prothrombin/antagonists & inhibitors, Reference Values, Thrombin/antagonists & inhibitors
Pubmed
Web of science
Create date
28/01/2008 11:38
Last modification date
28/01/2021 16:10
Usage data