Ximelagatran
(Synonyms: 希美加群,H 376/95) 目录号 : GC38332
A prodrug of melagatran, a thrombin inhibitor
Cas No.:192939-46-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Ximelagatran is an ester prodrug of melagatran, a potent, direct, and reversible thrombin inhibitor (Ki = 1.2 nM).1,2 While melagatran has poor oral bioavailability, ximelagatran displays good bioavailability resulting, in part, from rapid absorption at the gastrointestinal tract, as well as rapid onset of action.2 Ximelagatran is converted to melagatran by reduction and hydrolysis at the liver and other tissues.1,2 It is used as an anticoagulant in a variety of situations, including thromboembolic disorders, stroke prevention in atrial fibrillation, and therapy in vein thrombosis.2,3
1.Clement, B., and Lopian, K.Characterization of in vitro biotransformation of new, orally active, direct thrombin inhibitor ximelagatran, an amidoxime and ester prodrugDrug Metab. Dispos.31(5)645-651(2003) 2.Ho, S.J., and Brighton, T.A.Ximelagatran: Direct thrombin inhibitorVasc. Health Risk Manag.2(1)49-58(2006) 3.Ufer, M.Comparative pharmacokinetics of vitamin K antagonists warfarin, phenprocoumon and acenocoumarolClin. Pharmacokinet.44(12)1227-1246(2005)
| Cas No. | 192939-46-1 | SDF | |
| 别名 | 希美加群,H 376/95 | ||
| Canonical SMILES | O=C([C@@H]1CCN1C([C@@H](C2CCCCC2)NCC(OCC)=O)=O)NCC3=CC=C(C=C3)/C(N)=N/O | ||
| 分子式 | C24H35N5O5 | 分子量 | 473.57 |
| 溶解度 | DMSO: 250 mg/mL (527.91 mM); Methanol: 62.5 mg/mL (131.98 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1116 mL | 10.5581 mL | 21.1162 mL |
| 5 mM | 0.4223 mL | 2.1116 mL | 4.2232 mL |
| 10 mM | 0.2112 mL | 1.0558 mL | 2.1116 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Ximelagatran
Drugs Today (Barc) 2006 Jan;42(1):3-19.PMID:16511607DOI:10.1358/dot.2006.42.1.893611.
Despite the significant advances over the last 50 years with regard to anticoagulant therapy, warfarin remains the definitive standard for the long-term prevention of thromboembolic events in at-risk patients, except those with acute coronary syndromes, in which antiplatelets are preferred. Ximelagatran, a prodrug of melagatran, is an orally administered direct thrombin inhibitor whose therapeutic potential has been investigated in venous thromboembolism, acute coronary syndromes and prevention of stroke in atrial fibrillation. Clinical studies have demonstrated Ximelagatran to be comparable in efficacy to the oral vitamin K antagonist warfarin and low molecular weight heparin for prophylaxis of venous thromboembolism, comparable to warfarin for stroke prevention in the setting of atrial fibrillation, and, when combined with aspirin, more effective than aspirin alone at preventing major adverse cardiovascular events in patients with a recent myocardial infarction. Double-blind trials have also revealed the efficacy of Ximelagatran in the secondary prevention of venous thromboembolism and shown the agent to be as effective as enoxaparin/warfarin in treating patients with acute deep vein thrombosis. Adverse effects with Ximelagatran include elevations in alanine transaminase (ALT), which may require monitoring, and bleeding complications. Bleeding complications appear to be less than or at least comparable to those occurring with standard anticoagulant treatments like warfarin or low molecular weight heparin. In addition to its favorable efficacy and safety profile in comparison with standard anticoagulant therapy, the convenience of its oral, fixed-dose administration without the need for anticoagulation monitoring might help encourage a wider use of appropriate anticoagulation using Ximelagatran across the population at risk, reducing the incidence of thromboembolic events.
Ximelagatran/Melagatran: a review of its use in the prevention of venous thromboembolism in orthopaedic surgery
Drugs 2004;64(6):649-78.PMID:15018597DOI:10.2165/00003495-200464060-00010.
Ximelagatran (Exanta), the first available oral direct thrombin inhibitor, and its active form, melagatran, have been evaluated in the prevention of venous thromboembolism (VTE) in patients undergoing hip or knee replacement. After oral administration Ximelagatran is rapidly bioconverted to melagatran. Melagatran inactivates both circulating and clot-bound thrombin by binding to the thrombin active site, thus, inhibiting platelet activation and/or aggregation and reducing fibrinolysis time. The efficacy of subcutaneous melagatran followed by oral Ximelagatran has been investigated in four European trials and the efficacy of an all oral Ximelagatran regimen has been investigated in five US trials. In a dose-ranging European study, preoperatively initiated subcutaneous melagatran 3 mg twice daily followed by oral Ximelagatran 24 mg twice daily was significantly more effective than subcutaneous dalteparin sodium 5000IU once daily in preventing the occurrence of VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients undergoing hip or knee replacement. In one study, there were no significant differences in VTE prevention between subcutaneous melagatran 3 mg administered after surgery followed by Ximelagatran 24 mg twice daily and enoxaparin sodium (enoxaparin) 40 mg once daily. Compared with enoxaparin, significantly lower rates of proximal DVT and/or PE (major VTE) and total VTE were observed when melagatran was initiated preoperatively (2mg) then postoperatively (3mg) and followed by Ximelagatran 24 mg twice daily. In the US, four studies showed that postoperatively initiated Ximelagatran 24 mg twice daily was of similar efficacy to enoxaparin or warfarin in the prevention of VTE in patients undergoing hip or knee replacement. However, Ximelagatran 36 mg twice daily was superior to warfarin (target international normalised ratio of 2.5) at preventing the incidence of VTE in patients undergoing total knee replacement in two studies.Ximelagatran alone or after melagatran was generally well tolerated. Overall, the incidence of bleeding events and transfusion rates were not markedly different from those documented for comparator anticoagulants. In a post-hoc analysis of one study, transfusion rates were lower in Ximelagatran than enoxaparin recipients. Conclusions: Oral Ximelagatran alone or in conjunction with subcutaneous melagatran has shown good efficacy and was generally well tolerated in the prevention of VTE in patients undergoing orthopaedic surgery. Furthermore, patients receiving Ximelagatran/melagatran do not require anticoagulant monitoring. The drug has a low potential for drug interactions and can be administered either by subcutaneous injection or orally. Thus, on the basis of available evidence, Ximelagatran/melagatran appears poised to play an important role in the prophylaxis of VTE in patients undergoing orthopaedic surgery.
Ximelagatran in orthopaedic surgery
Pathophysiol Haemost Thromb 2005;34 Suppl 1:10-7.PMID:15812199DOI:10.1159/000083079.
Ximelagatran represents the first new oral anticoagulant since the introduction of warfarin almost 60 years ago, and has been evaluated for the treatment and prevention of a range of venous and arterial thromboembolic disorders. The MElagatran THRomboprophylaxis in Orthopaedic surgery (METHRO) and EXpanded PRophylaxis Evaluation Surgery Study (EXPRESS) studies have investigated the efficacy and safety of subcutaneous (s.c.) melagatran followed by oral Ximelagatran in preventing venous thromboembolism (VTE) in patients undergoing total hip replacement or total knee replacement. In METHRO II, immediate pre-operative-initiated s.c. melagatran followed by post-operative Ximelagatran dose-dependently reduced VTE, with the highest dose (melagatran 3 mg/Ximelagatran 24 mg twice daily) associated with a significantly reduced incidence of VTE compared with the low-molecular-weight heparin (LMWH) dalteparin (15.1 vs. 28.2%; p < 0.0001). In METHRO III, the efficacy of s.c. melagatran 3 mg/Ximelagatran 24 mg twice daily initiated post-operatively (4-12 h after surgery) was comparable to that of the LMWH enoxaparin initiated 12 h before surgery (total VTE incidence, 31.0 and 27.3%, respectively). Rates of severe bleeding were also comparable between treatments (melagatran/Ximelagatran = 1.4%; enoxaparin = 1.7%). Treatment with melagatran/Ximelagatran was significantly more effective when initiated earlier (4-8 h) rather than later (8-12 h) after surgery (total VTE incidence, 27.5 vs. 35.4%; p = 0.0034). Based on the results of METHRO II and III, the EXPRESS study evaluated the efficacy and bleeding profile of s.c. melagatran 2 mg immediately before surgery, followed by s.c. melagatran 3 mg on the evening of the day of surgery and then Ximelagatran 24 mg twice daily. This regimen was significantly more effective than enoxaparin (total VTE incidence, 20.3 vs. 26.6%; p < 0.0004). Excessive bleeding (as judged by the investigator) was more frequent with melagatran/Ximelagatran, but rates of fatal bleeding, critical-site bleeding and bleeding requiring re-operation did not differ between the groups. Taken together, the METHRO and EXPRESS studies demonstrate that melagatran/Ximelagatran has comparable or superior efficacy to LMWHs in the prevention of VTE in orthopaedic surgery patients, and that the timing and dose of melagatran is important in optimizing the balance of efficacy and bleeding risk.
Ximelagatran: a new type of oral anticoagulant
Int J Technol Assess Health Care 2005 Fall;21(4):480-6.PMID:16262971DOI:10.1017/S026646230505066X.
Objectives: This assessment sought to evaluate the comparative benefit and adverse effect profile of Ximelagatran, as well as the clinical issues surrounding its potential use. Methods: We performed a Dialog OneSearch across BIOSIS Previews, EMBASE, MEDLINE, PASCAL, and ToxFile to identify published literature. PubMed and The Cochrane Library were also searched. Gray literature was identified by searching a variety of Web sites of health technology assessment and related agencies and their associated databases. The manufacturer's Canadian office, AstraZeneca, was invited to submit information. Results: Ximelagatran is the first oral agent from a new class of anticoagulants called direct thrombin inhibitors. Other oral anticoagulants require routine blood monitoring; Ximelagatran does not. Ximelagatran has been evaluated in the areas of venous thromboembolism management, particularly after orthopedic surgery, and stroke prevention in patients with atrial fibrillation. Overall, Ximelagatran's efficacy appears comparable to other anticoagulants in these clinical settings. Also, bleeding rates were generally similar between Ximelagatran and comparators but, as for warfarin, bleeding risk increases with higher Ximelagatran doses. In addition, there is no specific antidote to help manage ximelagatran-induced bleeding. Finally, significantly more patients exposed to long-term Ximelagatran developed elevated liver enzymes more than three times the upper normal limit, compared with patients on comparator anticoagulants. Conclusions: Given its apparent simplicity of use, Ximelagatran carries the potential to replace, at least in part, anticoagulants currently used in the management of venous thromboembolism or for preventing stroke in atrial fibrillation patients. However, the safety of Ximelagatran will not be fully known without further evaluation and surveillance for potential liver toxicity. There is also a need to evaluate its use in special populations such as patients with renal failure and patients using several concurrent medications.
Ximelagatran: a new oral anticoagulant
Heart Dis 2003 Nov-Dec;5(6):397-408.PMID:14633322DOI:10.1097/01.hdx.0000099777.39577.e8.
Although there have been many significant advances over the last 50 years with regards to anticoagulant therapy, warfarin remains the definitive standard for the long-term prevention of thromboembolic events in many patients at risk for these complications. Although effective, warfarin has a narrow therapeutic window, necessitating frequent laboratory monitoring for anticoagulant effect. Ximelagatran is an investigational anticoagulant that directly inhibits thrombin, unlike heparin or warfarin, which are indirect inhibitors. Although indirect thrombin inhibitors are mainly only effective at inhibiting circulating thrombin, direct thrombin inhibitors are able to inhibit both free and clot-bound thrombin, thereby producing more effective anticoagulation. Ximelagatran is the first orally available direct thrombin inhibitor to reach phase 3 clinical trials. Ximelagatran is a prodrug for the active metabolite melagatran, and has been demonstrated to have a relatively wide therapeutic window in terms of bleeding and antithrombotic effect compared with warfarin. Clinical studies have demonstrated Ximelagatran to be comparable in efficacy to warfarin and low-molecular-weight heparins (LMWH) for prophylaxis of venous thromboembolism, comparable to warfarin for stroke prevention in the setting of atrial fibrillation, and, when combined with aspirin, possible more effective than aspirin alone at preventing major adverse cardiovascular events in patients with a recent myocardial infarction. Adverse effects with Ximelagatran primarily involve bleeding complications, which are more frequent than with placebo, but appear comparable to those occurring with standard anticoagulant treatment (ie, warfarin and LMWH). Ximelagatran has also been demonstrated to cause transient increases in liver enzymes, the significance of which will need to be addressed in ongoing phase 3 studies. Should ongoing trials prove Ximelagatran to have at least similar therapeutic efficacy and safety as warfarin, Ximelagatran may become a first-line anticoagulant due to its ease of administration and lack of a need for drug monitoring. The results of these trials are eagerly awaited in helping to defining the place in therapy for this promising new agent.