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Pharmacokinetics, pharmacodynamics and clinical effects of the oral direct thrombin inhibitor ximelagatran in acute treatment of patients with pulmonary embolism and deep vein thrombosis

Wahlander, K; Lapidus, L; Olsson, Carl-Gustav LU ; Thuresson, A; Eriksson, UG; Larson, G and Eriksson, H (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)
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author
organization
publishing date
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 Ltd
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
2007-11-09 15:00:44
date last changed
2017-09-03 03:45:51
@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},
  keyword      = {ximelagatran,thrombosis,deep vein,oral direct thrombin inhibitor,pulmonary embolism,venous thromboembolism},
  language     = {eng},
  number       = {3-4},
  pages        = {93--99},
  publisher    = {Elsevier Ltd},
  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},
  volume       = {107},
  year         = {2002},
}