Pharmacokinetic properties of LMW-heparin-tyramine fractions with high or low affinity to antithrombin III in the rat.
Semin Thromb Hemost
; 23(1): 31-7, 1997.
Article
en En
| MEDLINE
| ID: mdl-9156408
We have recently presented evidence that a macrophage scavenger receptor-mediated pathway is responsible for the hepatic uptake of unfractionated heparins and low-molecular-weight heparins (LMWHs) in the rat. The same receptor-mediated pathway was partially responsible for the removal of oxidized low-density lipoprotein. Unfractionated and fractionated LMWHs exert their anticoagulatory effects predominately by reversibly binding to the plasma glycoprotein antithrombin III. In this study LMWHs modified by endpoint attachment of tyramine were radiolabeled and their fractions with low or high affinity to AT-III studied in vivo in rats. The high-affinity fraction was predominately cleared from the circulation by a hepatic uptake mechanism. About 25% of the injected high-affinity tracer material was recovered, whereas only about 8% of the low-affinity material was found in the liver after 180 minutes. Blocking the scavenger receptor-mediated liver RES uptake mechanism by maleylated bovine serum albumin led to a considerable decline in liver uptake (9 versus 25%). The low-affinity material was rapidly eliminated into the urine after 180 minutes. About 45% of the low-affinity material was excreted versus 23% of the high-affinity material. Tight binding to AT-III prevented LMWH-tyramine from being rapidly cleared from the circulation via the kidneys into the urine; instead, the scavenger receptor-mediated hepatic uptake mechanism seemed to be more dominant in removing material with high affinity to AT-III from blood.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antitrombina III
/
Receptores de Lipoproteína
/
Heparina de Bajo-Peso-Molecular
/
Proteínas de la Membrana
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Semin Thromb Hemost
Año:
1997
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Estados Unidos