当前位置： SCI文献检索 > JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS期刊下所有文献 > Repeated Oral or Subcutaneous LMWH Has similar Antithrombotic Activity in a Rat Venous Thrombosis Model: Antithrombotic Activity Correlates With Heparin on Endothelium When Orally Administered.

Repeated Oral or Subcutaneous LMWH Has similar Antithrombotic Activity in a Rat Venous Thrombosis Model: Antithrombotic Activity Correlates With Heparin on Endothelium When Orally Administered.

Abstract：

:Low-molecular-weight heparins (LMWHs) endure as important drugs for thromboprophylaxis. Although clinical use relies on the subcutaneous (SC) route, our previous studies show that single-dose orally administered LMWHs have antithrombotic activity. Since thromboprophylaxis requires long-term treatment, we examined antithrombotic effects of subacute oral LMWHs in a rat venous thrombosis model and compared results to SC or single-dose oral administration. We measured LMWH in endothelium and plasma, weight change and complete blood counts (CBC). Oral LMWH tinzaparin (3 × 0.1 mg/kg/12 or 24 hours) or reviparin (3 × 0.025 mg/kg/24 hours) significantly decreased thrombosis compared to saline. In the subacute study (60 × 0.1 mg/kg/12 hours), oral or SC tinzaparin significantly reduced thrombosis compared to saline but not to single or 3 × 0.1 mg/kg/12 hours oral tinzaparin. Antithrombotic effects were similar between oral and SC administration. LMWH was found on endothelium following oral but not SC administration. Endothelial concentrations were significantly correlated with incidence of stable thrombi ( P = 0.021 and 0.04 for aortic and vena cava endothelium respectively, χ2 test) and total thrombi ( P = 0.003 for vena cava endothelium). Anti-Xa activity was significantly greater for oral or SC LMWH than saline and significantly greater for SC versus oral LMWH. Values for CBCs were within normal ranges (mean ± 2 SD). There was no evidence of bleeding. Weight gain was similar between groups. In conclusion, subacute oral and SC LMWH have similar antithrombotic effects. Antithrombotic activity with oral administration is correlated with endothelial LMWH concentrations but not with plasma anticoagulant activity.

journal_name

J Cardiovasc Pharmacol Ther

journal_title

Journal of cardiovascular pharmacology and therapeutics

authors

Hiebert LM

doi

10.1177/1074248416667601

subject

Has Abstract

pub_date

2017-05-01 00:00:00

pages

264-272

issue

eissn

1074-2484

issn

1940-4034

pii

1074248416667601

journal_volume

pub_type

杂志文章

在线工具

Repeated Oral or Subcutaneous LMWH Has similar Antithrombotic Activity in a Rat Venous Thrombosis Model: Antithrombotic Activity Correlates With Heparin on Endothelium When Orally Administered.