Evidence for a saturable mechanism of disappearance of standard heparin in rabbits

Journal Article · Mon Jun 15 00:00:00 EDT 1987 · Thromb. Res.; (United States)

DOI:https://doi.org/10.1016/0049-3848(87)90075-2· OSTI ID:6076753

Boneu, B; Caranobe, C; Gabaig, A M; Dupouy, D; Sie, P; Buchanan, M R; Hirsh, J

This work demonstrates that after bolus intravenous injection standard heparin (SH) disappearance results from the combination of a saturable and a non saturable mechanism. Pharmacokinetics and pharmacodynamics of SH were studied by measuring the disappearance of increasing doses (5 - 500 anti-factor Xa U/kg) of /sup 125/I-heparin and of its biological effects. CPM curves allowed the determination of the half lives of heparin according to the dose injected. The half lives were clearly dose dependent and reached a plateau over 100 anti-factor Xa U/kg. The complex curve which describes the amount of heparin cleared per time unit after any given dose has been resolved into its two components reflecting a saturable and a non saturable mechanism of disappearance. For the doses less than 100 anti-factor Xa U/kg the saturable mechanism was preeminent and the anti-factor Xa activity disappearance followed an exponential pattern; for the doses less than 100 anti-factor Xa U/kg the contribution of the non saturable mechanism becomes more important and the anti-factor Xa activity disappearance followed a concave-convex pattern. Further experiments showed that the heparin half life shortened as the circulating anti-factor Xa activity decreased; this phenomenon may explain the concave-convex pattern of the curve of the anticoagulant effect observed after injection of large doses of SH.

• Research Organization: Centre de Transfusion Sanguine Toulouse, France
• OSTI ID: 6076753
• Journal Information: Thromb. Res.; (United States), Journal Name: Thromb. Res.; (United States) Vol. 46:6; ISSN THBRA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMALS
ANTICOAGULANTS
BETA DECAY RADIOISOTOPES
BIOLOGICAL HALF-LIFE
BODY BURDEN
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
MUCOPOLYSACCHARIDES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
POLYSACCHARIDES
RABBITS
RADIOISOTOPES
SACCHARIDES
TRACER TECHNIQUES
VERTEBRATES