Pharmacokinetics, pharmacodynamics and clinical effects of the oral direct thrombin inhibitor ximelagatran in acute treatment of patients with pulmonary embolism and deep vein thrombosis
(2002) In Thrombosis Research 107(3-4). p.93-99- Abstract
- Introduction: Ximelagatran is a novel, oral direct thrombin inhibitor that is currently being investigated for the prophylaxis and treatment of thromboembolic events. This study evaluated the pharmacokinetics, pharmacodynamics, and clinical effects of melagatran, the active form of ximelagatran, in patients with both deep vein thrombosis (DVT) and pulmonary embolism (PE). Materials and methods: In this open-label study, 12 patients received a fixed dose of 48 mg oral ximelagatran twice daily for 6-9 days. Plasma samples were collected for determination of melagatran concentrations and scintigraphic changes and adverse events were recorded. Results: Peak plasma concentrations of melagatran were attained approximately 2 h after... (More)
- Introduction: Ximelagatran is a novel, oral direct thrombin inhibitor that is currently being investigated for the prophylaxis and treatment of thromboembolic events. This study evaluated the pharmacokinetics, pharmacodynamics, and clinical effects of melagatran, the active form of ximelagatran, in patients with both deep vein thrombosis (DVT) and pulmonary embolism (PE). Materials and methods: In this open-label study, 12 patients received a fixed dose of 48 mg oral ximelagatran twice daily for 6-9 days. Plasma samples were collected for determination of melagatran concentrations and scintigraphic changes and adverse events were recorded. Results: Peak plasma concentrations of melagatran were attained approximately 2 h after administration of ximelagatran. Melagatran plasma concentration profiles were similar on Days 1, 2, and 6-9. Plasma activated partial thromboplastin time increased following administration of ximelagatran and reached a peak that was approximately twofold higher than the predose activated partial thromboplastin time and correlated with melagatran plasma concentrations (R-2 = 0.69). All but one patient (with malignancy) showed regressed or unchanged lung scintigraphic findings, and six of these demonstrated no, or only minor, perfusion defects at central evaluation after 6-9 days of ximelagatran treatment. Clinical symptoms, including chest pain, dyspnoea, cough, and oedema, and pain in the affected leg, were improved. Ximelagatran was well tolerated with no deaths or severe bleeding events reported during treatment. Conclusion: Treatment with a fixed dose of oral ximelagatran, used without routine coagulation monitoring, showed reproducible pharmacokinetics and pharmacodynamics with a rapid onset of action and promising clinical results in patients with pulmonary embolism. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/322134
- author
- Wahlander, K ; Lapidus, L ; Olsson, Carl-Gustav LU ; Thuresson, A ; Eriksson, UG ; Larson, G and Eriksson, H
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- ximelagatran, thrombosis, deep vein, oral direct thrombin inhibitor, pulmonary embolism, venous thromboembolism
- in
- Thrombosis Research
- volume
- 107
- issue
- 3-4
- pages
- 93 - 99
- publisher
- Elsevier
- external identifiers
-
- pmid:12431473
- wos:000179566500002
- scopus:0037104691
- ISSN
- 1879-2472
- DOI
- 10.1016/S0049-3848(02)00259-1
- language
- English
- LU publication?
- yes
- id
- 57e18be0-151a-4daf-9de2-57495dc83427 (old id 322134)
- date added to LUP
- 2016-04-01 12:03:13
- date last changed
- 2022-04-13 05:21:30
@article{57e18be0-151a-4daf-9de2-57495dc83427,
abstract = {{Introduction: Ximelagatran is a novel, oral direct thrombin inhibitor that is currently being investigated for the prophylaxis and treatment of thromboembolic events. This study evaluated the pharmacokinetics, pharmacodynamics, and clinical effects of melagatran, the active form of ximelagatran, in patients with both deep vein thrombosis (DVT) and pulmonary embolism (PE). Materials and methods: In this open-label study, 12 patients received a fixed dose of 48 mg oral ximelagatran twice daily for 6-9 days. Plasma samples were collected for determination of melagatran concentrations and scintigraphic changes and adverse events were recorded. Results: Peak plasma concentrations of melagatran were attained approximately 2 h after administration of ximelagatran. Melagatran plasma concentration profiles were similar on Days 1, 2, and 6-9. Plasma activated partial thromboplastin time increased following administration of ximelagatran and reached a peak that was approximately twofold higher than the predose activated partial thromboplastin time and correlated with melagatran plasma concentrations (R-2 = 0.69). All but one patient (with malignancy) showed regressed or unchanged lung scintigraphic findings, and six of these demonstrated no, or only minor, perfusion defects at central evaluation after 6-9 days of ximelagatran treatment. Clinical symptoms, including chest pain, dyspnoea, cough, and oedema, and pain in the affected leg, were improved. Ximelagatran was well tolerated with no deaths or severe bleeding events reported during treatment. Conclusion: Treatment with a fixed dose of oral ximelagatran, used without routine coagulation monitoring, showed reproducible pharmacokinetics and pharmacodynamics with a rapid onset of action and promising clinical results in patients with pulmonary embolism.}},
author = {{Wahlander, K and Lapidus, L and Olsson, Carl-Gustav and Thuresson, A and Eriksson, UG and Larson, G and Eriksson, H}},
issn = {{1879-2472}},
keywords = {{ximelagatran; thrombosis; deep vein; oral direct thrombin inhibitor; pulmonary embolism; venous thromboembolism}},
language = {{eng}},
number = {{3-4}},
pages = {{93--99}},
publisher = {{Elsevier}},
series = {{Thrombosis Research}},
title = {{Pharmacokinetics, pharmacodynamics and clinical effects of the oral direct thrombin inhibitor ximelagatran in acute treatment of patients with pulmonary embolism and deep vein thrombosis}},
url = {{http://dx.doi.org/10.1016/S0049-3848(02)00259-1}},
doi = {{10.1016/S0049-3848(02)00259-1}},
volume = {{107}},
year = {{2002}},
}