Pharmacokinetics and pharmacodynamics of the dual FII/FX inhibitor BIBT 986 in endotoxin-induced coagulation
Clinical Pharmacology and Therapeutics, ISSN: 0009-9236, Vol: 81, Issue: 6, Page: 858-866
2007
- 18Citations
- 20Captures
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Metrics Details
- Citations18
- Citation Indexes18
- CrossRef18
- 17
- Captures20
- Readers20
- 20
Article Description
BIBT986 is a dual inhibitor of factors Xa and IIa. The aim of this study was to compare with placebo the effect of three doses of BIBT986 on coagulation, platelet activation, and inflammation. This was a prospective, randomized, double-blind, placebo-controlled, parallel-group dose escalation trial in 48 healthy male volunteers. Participants received one of three doses of BIBT986 or placebo intravenously together with a bolus infusion of 2 ng/kg lipopolysaccharide (LPS). BIBT986 dose-dependently changed global coagulation parameters and in vivo markers of thrombin generation and action: BIBT986 doses, which prolonged activated partial thromboplastin time by 100%, completely suppressed the LPS-induced increases in prothrombin fragment, thrombin-antithrombin complexes, and D-dimer, which were 6.1-, 14.5, and 3.5-fold in the placebo group, respectively. BIBT986 did not influence inflammation, fibrinolysis, or platelet activation. Therefore, BIBT986 is a potent anticoagulant in the human endotoxemia model.
Bibliographic Details
Wiley
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