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Thromb Haemost 2002; 87(02): 300-305
DOI: 10.1055/s-0037-1612989
Letters to the Editor
Schattauer GmbH

Inhibition of Thrombin Generation by the Oral Direct Thrombin Inhibitor Ximelagatran in Shed Blood from Healthy Male Subjects

Troy C. Sarich
1   AstraZeneca R&D Mölndal, Mölndal, Sweden
,
Ulf G. Eriksson
1   AstraZeneca R&D Mölndal, Mölndal, Sweden
,
Christer Mattsson
1   AstraZeneca R&D Mölndal, Mölndal, Sweden
,
Michael Wolzt
2   Department of Clinical Pharmacology, Allgemeines Krankenhaus Wien, University of Vienna, Austria
,
Lars Frison
1   AstraZeneca R&D Mölndal, Mölndal, Sweden
,
Gunnar Fager
1   AstraZeneca R&D Mölndal, Mölndal, Sweden
,
David Gustafsson
1   AstraZeneca R&D Mölndal, Mölndal, Sweden
› Author Affiliations
Further Information

Publication History

Received 27 September 2001

Accepted after revision 16 November 2001

Publication Date:
13 December 2017 (online)

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Summary

Ximelagatran, an oral direct thrombin inhibitor, whose active form is melagatran, was studied using a model of thrombin generation in humans. Healthy male volunteers (18 per group) received ximelagatran (60 mg p.o.), dalteparin (120 IU/kg s.c.) or a control (water p.o.). Shed blood, collected after incision of the forearm with standardised bleeding time devices at pre-dose, and at 2, 4 and 10 h post-dosing, was analysed for markers of thrombin generation. Statistically significant reductions (p < 0.05) in levels of prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) in shed blood were detected at 2 and 4 h post-dosing in both the ximelagatran and dalteparin groups. Shed blood F1+2 and TAT levels had returned to pre-dose levels at 10 h post-dosing. Using a shed blood model, we demonstrate that the reversible thrombin inhibitor melagatran and, therefore, oral administration of ximelagatran, inhibits thrombin generation in humans after acute activation of coagulation.

Keywords

Oral direct thrombin inhibitor - ximelagatran - melagatran - thrombin generation - shed blood
 

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