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Disappearance of a low molecular weight heparin fraction (CY 216) differs from standard heparin in rabbits

Journal Article · · Thromb. Res.; (United States)
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In previous studies, we have reported that standard heparin (SH) was cleared by two mechanisms, a saturable mechanism which predominated at low doses (less than 100 anti-factor Xa U/kg) and a non-saturable mechanism which predominated at higher doses, when the first mechanism became saturated. In this study, we examined the importance of these two mechanisms in the disappearance of a low molecular weight heparin fraction (LMWH) (CY 216), by comparing the pharmacokinetics and the pharmacodynamics of a wide range of doses of SH and CY 216 (1.5 to 500 anti-factor Xa U/kg). Pharmacokinetics was measured as the disappearance of /sup 125/I-radiolabelled SH or CY 216. Pharmacodynamics was measured as the disappearance of the anti-factor Xa activity of SH and CY 216. We found that the saturable mechanism contributed little to the disappearance of CY 216 and that it was cleared predominantly by the non-saturable mechanism at all doses tested. Thus, at low doses (less than 100 anti-factor Xa U/kg), SH was cleared more rapidly than CY 216, whereas at higher doses, CY 216 was cleared more rapidly than SH. We conclude that the mechanism of disappearance of LMWH's differ significantly from those of SH, and that this difference may explain the apparent prolonged anticoagulant activity of LMWH's within the therapeutic range doses.

Research Organization:
Centre de Transfusion Sanguine, Toulouse, France
OSTI ID:
6026817
Journal Information:
Thromb. Res.; (United States), Journal Name: Thromb. Res.; (United States) Vol. 46:6; ISSN THBRA
Country of Publication:
United States
Language:
English

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Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMALS
ANTICOAGULANTS
BETA DECAY RADIOISOTOPES
CARBOHYDRATES
CLEARANCE
DAYS LIVING RADIOISOTOPES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
HEMATOLOGIC AGENTS
HEPARIN
INJECTION
INTAKE
INTERMEDIATE MASS NUCLEI
INTRAVENOUS INJECTION
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
METABOLISM
MOLECULAR WEIGHT
MUCOPOLYSACCHARIDES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
POLYSACCHARIDES
RABBITS
RADIOISOTOPES
SACCHARIDES
TRACER TECHNIQUES
VERTEBRATES