Document Detail


Pharmacokinetics of heparin and low molecular weight heparin.
MedLine Citation:
PMID:  2176903     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
After parenteral injection, heparin is removed from the blood via two mechanisms, saturable and non-saturable. The saturable mechanism represents clearance by the reticuloendothelial system and endothelial cells, to which heparin binds with a high affinity. The non-saturable mechanism is represented by renal excretion. The contribution of the two mechanisms to the clearance of heparin varies according to the dose delivered and the molecular weight of the heparin preparation. At low doses, unfractionated heparin (UH) is removed mainly via the saturable mechanism, while at higher doses the contribution of the non-saturable mechanism to its clearance becomes pre-eminent. This model accounts for the major pharmacokinetic properties of UH. After bolus intravenous injection of low doses, UH disappears from the blood exponentially with a dose-dependent half-life; at higher doses, UH disappears with a concave-convex pattern. Under continuous intravenous infusion there is a non-linear relationship between the dose of UH injected and the steady-state plasma concentration. After subcutaneous injection, the bioavailability of the anti-factor Xa activity increases with the dose delivered and tends toward 100% at high doses. In contrast, low molecular weight heparins (LMWH) are mainly removed by non-saturable renal excretion. This explains the dose independence of the pharmacokinetic parameters of LMWH, the excellent bioavailability of the subcutaneous route at any dose, and the prolongation of LMWH half-life in cases of chronic renal insufficiency. However, the model does not explain the large interindividual variability of the pharmacokinetic parameters of both UH and LMWH.
Authors:
B Boneu; C Caranobe; P Sie
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Baillière's clinical haematology     Volume:  3     ISSN:  0950-3536     ISO Abbreviation:  Baillieres Clin. Haematol.     Publication Date:  1990 Jul 
Date Detail:
Created Date:  1991-02-28     Completed Date:  1991-02-28     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8800474     Medline TA:  Baillieres Clin Haematol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  531-44     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Availability
Factor Xa / antagonists & inhibitors
Half-Life
Heparin / administration & dosage,  pharmacokinetics*,  pharmacology
Heparin, Low-Molecular-Weight / administration & dosage,  pharmacokinetics*,  pharmacology
Humans
Injections, Intravenous
Injections, Subcutaneous
Kidney / metabolism
Kidney Failure, Chronic / metabolism
Metabolic Clearance Rate
Mononuclear Phagocyte System / metabolism
Rabbits
Chemical
Reg. No./Substance:
0/Heparin, Low-Molecular-Weight; 9005-49-6/Heparin; EC 3.4.21.6/Factor Xa

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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