Abstract
Ximelagatran is an oral direct thrombin inhibitor (DTI), the active form of which is melagatran. Approximately 20% of an oral ximelagatran dose becomes bioavailable as melagatran, which binds noncovalently and reversibly to both fibrin-bound and freely circulating thrombin. Oral ximelagatran dosing not only inhibits thrombin activity rapidly, competitively, and potently, but also delays and suppresses thrombin generation. In humans, oral ximelagatran exhibits anticoagulant, antiplatelet, and profibrinolytic effects, with only minor prolongation of the capillary bleeding time. Oral ximelagatran exhibits a stable and predictable pharmacokinetic profile during repeated dosing, with low intra- and inter-individual variation, and a low potential for interaction with other medications. It is excreted primarily as melagatran via the kidney, without unexpected bioaccumulation. Dosing requirements do not vary with age, gender, ethnicity, obesity, or food or alcohol intake. Clinical trials (total n > 30,000) have evaluated oral ximelagatran in four indications: the prevention of venous thromboembolism (VTE, comprising deep venous thrombosis with or without and pulmonary embolism) after elective hip- or knee-replacement surgery (with approval granted by France, as the Reference Member State for the European Union); treatment and long-term secondary prevention of VTE; the prevention of stroke and other systemic embolic events associated with nonvalvular atrial fibrillation; and the prevention of cardiovascular events after an acute myocardial infarction. The results of these trials suggest that the benefit-risk profile of oral ximelagatran therapy, administered at a fixed-dose without coagulation monitoring, compares favorably with that of currently approved standard therapy.
Keywords: ximelagatran, melagatran, direct thrombin inhibitors, anticoagulation, antithrombotic agents, oral administration, thromboembolism
Current Pharmaceutical Design
Title: Ximelagatran - A Promising New Drug in Thromboembolic Disorders
Volume: 11 Issue: 4
Author(s): Palle Petersen
Affiliation:
Keywords: ximelagatran, melagatran, direct thrombin inhibitors, anticoagulation, antithrombotic agents, oral administration, thromboembolism
Abstract: Ximelagatran is an oral direct thrombin inhibitor (DTI), the active form of which is melagatran. Approximately 20% of an oral ximelagatran dose becomes bioavailable as melagatran, which binds noncovalently and reversibly to both fibrin-bound and freely circulating thrombin. Oral ximelagatran dosing not only inhibits thrombin activity rapidly, competitively, and potently, but also delays and suppresses thrombin generation. In humans, oral ximelagatran exhibits anticoagulant, antiplatelet, and profibrinolytic effects, with only minor prolongation of the capillary bleeding time. Oral ximelagatran exhibits a stable and predictable pharmacokinetic profile during repeated dosing, with low intra- and inter-individual variation, and a low potential for interaction with other medications. It is excreted primarily as melagatran via the kidney, without unexpected bioaccumulation. Dosing requirements do not vary with age, gender, ethnicity, obesity, or food or alcohol intake. Clinical trials (total n > 30,000) have evaluated oral ximelagatran in four indications: the prevention of venous thromboembolism (VTE, comprising deep venous thrombosis with or without and pulmonary embolism) after elective hip- or knee-replacement surgery (with approval granted by France, as the Reference Member State for the European Union); treatment and long-term secondary prevention of VTE; the prevention of stroke and other systemic embolic events associated with nonvalvular atrial fibrillation; and the prevention of cardiovascular events after an acute myocardial infarction. The results of these trials suggest that the benefit-risk profile of oral ximelagatran therapy, administered at a fixed-dose without coagulation monitoring, compares favorably with that of currently approved standard therapy.
Export Options
About this article
Cite this article as:
Petersen Palle, Ximelagatran - A Promising New Drug in Thromboembolic Disorders, Current Pharmaceutical Design 2005; 11 (4) . https://dx.doi.org/10.2174/1381612053382016
DOI https://dx.doi.org/10.2174/1381612053382016 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Recent Development on Anti-Obesity Compounds and their Mechanisms of Action: A Review
Current Medicinal Chemistry Vascular effects of flavonoids
Current Medicinal Chemistry Incretin-Based Therapies, Glucometabolic Health and Endovascular Inflammation
Current Pharmaceutical Design Epidemiology of Major Congenital Malformations with Specific Focus on Teratogens
Current Drug Safety Open Questions about Pulmonary Hypertension and Exercise Training: A Critical Review
Current Respiratory Medicine Reviews High Density Lipoprotein Associated Paraoxonase1 Activity in Relation to Oxidative Stress in CAD Patients
Current Cardiology Reviews microRNA-133: Expression, Function and Therapeutic Potential in Muscle Diseases and Cancer
Current Drug Targets Triglycerides and Vascular Risk: Insights from Epidemiological Data and Interventional Studies
Current Drug Targets Coronary Angiography Using Noninvasive Imaging Techniques of Cardiac CT and MRI
Current Cardiology Reviews The Role of Venous Abnormalities in Neurological Disease
Reviews on Recent Clinical Trials Novel Strategies for the Management of Acute Decompensated Heart Failure
Current Cardiology Reviews Pharmacological Drug Delivery Strategies for Improved Therapeutic Effects: Recent Advances
Current Pharmaceutical Design Antipsoriatic Drug Development: Challenges and New Emerging Therapies
Recent Patents on Inflammation & Allergy Drug Discovery High-Throughput Functional Genomic Methods to Analyze the Effects of Dietary Lipids
Current Pharmaceutical Biotechnology Pathogenetic Pathways of Cardiorenal Syndrome and their Possible Therapeutic Implications
Current Pharmaceutical Design Melatonin, a Potential Therapeutic Agent for Smooth Muscle-Related Pathological Conditions and Aging
Current Medicinal Chemistry Mobile Phone Based Biomedical Imaging Technology: A Newly Emerging Area
Recent Patents on Biomedical Engineering (Discontinued) ω-3 Polyunsaturated Fatty Acids Effects on the Cardiometabolic Syndrome and their Role in Cardiovascular Disease Prevention: An Update from the Recent Literature
Recent Advances in Cardiovascular Drug Discovery (Discontinued) Structural Neuroimaging Findings in Major Depressive Disorder Throughout Aging: A Critical Systematic Review of Prospective Studies
CNS & Neurological Disorders - Drug Targets Patent Selections
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery