Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reteplase (r-PA) is a genetically engineered deletion mutant of wild-type tissue-type plasminogen activator. The structural differences lead to different functional properties, such as a prolonged half-life. The compound demonstrated good thrombolytic efficacy in in vitro as well as in animal studies. In angiographically controlled patency studies (GRECO, GRECO-2 RAPID-1, RAPID-2), the double-bolus application scheme was established, and a superior patency profile for reteplase in comparison to alteplase was demonstrated. Mortality studies established reteplase as a safe drug with a 30-day mortality at least equivalent to streptokinase (INJECT) and very similar to alteplase (GUSTO-3). A possible advantage may be the double-bolus application without a need for weight adjustment, especially in a prehospital setting. Thus, reteplase can be regarded as an excellent alternative to streptokinase or alteplase for thrombolytic therapy in acute myocardial infarction.
 ...
PMID:Reteplase (r-PA): a new plasminogen activator. 1598 67

There are no reliable data on plasmin or plasminogen activator (PA) activities in blood of patients receiving fibrinolytic treatment. This is due to continuing in vitro action of PA after blood withdrawal. These artefactual changes of PA or plasmin activities have been prevented by arginine stabilization of blood samples of myocardial infarction patients treated with plasminogen activators. Twelve patients with myocardial infarction were treated with reteplase 2 x 10,000,000 units in bolus application; one patient was treated with 100 mg t-PA in continuous infusion. Blood was immediately stabilized with EDTA and arginine. The plasma was analyzed with newly developed assays for plasmin and PA. Maximal plasmin activities in blood were obtained at 40 to 60 minutes reteplase treatment time (0.1-0.6 U/mL = approximately 0.05-0.3 micromol/L plasmin). The 50% clearance rate for plasmatic Pli was greater than 30 minutes. The plasmatic reteplase concentration peaked at approximately 2,000 U/mL after the first bolus infusion and at approximately 1,500-3,500 U/mL after the second bolus infusion. Reteplase was cleared to 50% within less than 30 minutes, also with great inter-individual variation. Arginine stabilization of blood allows reliable determinations of activities of plasmin and PA in blood of patients under fibrinolytic treatment: substantial plasmin activities occur in patients treated by reteplase. Therapeutic thrombolysis might be improved, imitating the physiologic cellular thrombolysis; i.e., polymorphonuclear phagocytes (PMN) that can be activated by singlet oxygen ((1)O(2)). PMN might be superior to PA in selective lysis of pathologic thrombi.
 ...
PMID:Monitoring of plasmin and plasminogen activator activity in blood of patients under fibrinolytic treatment by reteplase. 1670 24

Alteplase, an intravenously administered form of recombinant tissue plasminogen activator (rt-PA), remains the only US FDA-approved thrombolytic treatment for acute ischemic stroke within 3 h of symptom onset. Patients treated with intravenous rt-PA are at least 30% more likely to have minimal or no disability at 3 months compared with placebo. Despite an increased risk of symptomatic intracranial hemorrhage, rt-PA does not increase mortality. The benefit achieved with rt-PA is cost effective and sustained 1 year after treatment. Despite its clear benefit, rt-PA remains underutilized. Although the future of acute ischemic stroke treatment will most likely involve a multi-faceted treatment approach, the primary objective remains to establish recanalization of the involved vessel. For patients with acute ischemic stroke within the first 3 h of symptom onset, rt-PA remains the first step in accomplishing this goal.
 ...
PMID:Alteplase for acute ischemic stroke. 1671 92

Reteplase (Retavase) is a plasminogen activator, mimicking endogenous tissue plasminogen activator (t-PA), a serine protease, converting plasminogen to plasmin and thereby precipitating thrombolysis. It is a third-generation recombinant form of t-PA that operates in the presence of fibrin (i.e. it is fibrin specific). Reteplase can be administered as a bolus dose (nonweight-based) rather than an infusion, which promotes rapid and safe administration. The ease of administration of this reteplase dosage regimen (two 10U bolus doses, each over 2 minutes, 30 minutes apart) is conducive to prehospital initiation of thrombolytic treatment in patients with ST-segment elevation myocardial infarction (STEMI), which reduces the time to treatment, a critical factor in improving long-term survival. In large randomized clinical trials of patients with STEMI, reteplase was superior to alteplase for coronary artery patency (according to TIMI [thrombolysis in myocardial infarction] flow) at 60 and 90 minutes, but there was no significant difference between agents for mortality rate and incidence of intracranial bleeding. The 35-day mortality rates were equivalent for reteplase and streptokinase recipients; there was reduced incidence of some cardiac events with reteplase versus streptokinase, but a greater incidence of hemorrhagic stroke. Reteplase has also shown thrombolytic efficacy (in nonapproved indications) as a catheter-directed intra-arterial or intravenous infusion for peripheral vessel occlusions, as 5-minute bolus doses (in 1U increments) for acute ischemic stroke, as a low-dose solution for occluded catheters or grafts, and as an intravenous double bolus for massive pulmonary embolism. Across studies in these indications, the incidence of bleeding complications associated with reteplase treatment appeared to be similar to that associated with other thrombolytic agents. With its efficacy, and the ease of administration of the bolus doses potentially minimizing dosage errors when treatment is administered under time pressure, reteplase is a valuable option for pre- or in-hospital thrombolytic treatment in patients with STEMI, and is a useful thrombolytic for the treatment of the other thrombotic occlusive disorders described.
 ...
PMID:Reteplase: a review of its use in the management of thrombotic occlusive disorders. 1691 28

Reteplase (Retavase) is a plasminogen activator, mimicking endogenous tissue plasminogen activator (t-PA), a serine protease, converting plasminogen to plasmin and thereby precipitating thrombolysis. It is a third-generation recombinant form of t-PA that operates in the presence of fibrin (i.e. it is fibrin specific). Reteplase can be administered as a bolus dose (nonweight-based), rather than an infusion, which promotes rapid and safe administration. The ease of administration of this reteplase dosage regimen (two 10U bolus doses, each over 2 minutes, 30 minutes apart) is conducive to prehospital initiation of thrombolytic treatment in patients with ST-segment elevation myocardial infarction (STEMI), which reduces the time to treatment, a critical factor in improving long-term survival. In large randomized clinical trials of patients with STEMI, reteplase was superior to alteplase for coronary artery patency (according to TIMI [thrombolysis in myocardial infarction] flow) at 60 and 90 minutes, but there was no significant difference between agents for mortality rate and incidence of intracranial bleeding. The 35-day mortality rates were equivalent for reteplase and streptokinase recipients; there was reduced incidence of some cardiac events with reteplase versus streptokinase, but a greater incidence of hemorrhagic stroke. Reteplase has also shown thrombolytic efficacy (in nonapproved indications) as a catheter-directed intra-arterial or intravenous infusion for peripheral vessel occlusions, as 5-minute bolus doses (in 1U increments) for acute ischemic stroke, as a low-dose solution for occluded catheters or grafts, and as an intravenous double bolus for massive pulmonary embolism. Across studies in these indications, the incidence of bleeding complications associated with reteplase treatment appeared to be similar to that associated with other fibrin-specific thrombolytic agents. With its efficacy, and the ease of administration of the bolus doses potentially minimizing dosage errors when treatment is administered under time pressure, reteplase is a valuable option for pre- or in-hospital thrombolytic treatment in patients with STEMI, and is a useful thrombolytic for the treatment of the other thrombotic occlusive disorders described.
 ...
PMID:Spotlight on reteplase in thrombotic occlusive disorders. 1726 91

Favorable outcome by hyperacute rt-PA (recombinant tissue-type plasminogen activator) therapy was suggested firstly by randomized controlled trials (RCT) in Japan, and confirmed by the NINDS trial (1995) using alteplase within the initial 3 hours. A phase III clinical trial using open-labeled, single-dose alteplase was carried out in Japan (Japan Alteplase Clinical Trial, J-ACT). The study protocol was almost compatible to that of the NINDS study, except for several modifications including lower dose administration of alteplase (0.6 mg/kg) in the J-ACT than that in the NINDS study (0.9 mg/kg). The clinical backgrounds were almost similar, and frequencies of very favorable outcome at 3-months and symptomatic intracranial hemorrhage were comparable between the studies. The Japanese Government approved the use of intravenous alteplase therapy in October 11, 2005. The Japan Stroke Society published a guideline and gave more than 130 courses for appropriate alteplase therapy immediately after the approval. Clinical results of this therapy were excellent in the initial 21 cases of our hospital. New approaches will open the door to an exciting new era for stroke management. They include MR-based delayed thrombolysis up to 9 hours after stroke onset and ultrasound-enhanced systemic thrombolysis.
 ...
PMID:[Thrombolytic therapy]. 1743 95

We report a case of intracardiac thrombus in a patient supported by the Jarvik 2000 Flowmaker successfully treated with a single dose of peripherally administered TNK-tissue plasminogen activator (Tenecteplase, Metalyse, Boehringer Ingelheim). This strategy may be considered in the case of life-threatening VAD associated thrombosis to avoid the need for intracardiac drug delivery or VAD replacement. We also discuss the apparent increased thrombotic risk in patients receiving a VAD for chemotherapy induced cardiomyopathy and the implications this may have for the choice of VAD.
 ...
PMID:Successful treatment of ventricular assist device associated ventricular thrombus with systemic tenecteplase. 1758 87

We incorporated diffusion-weighted magnetic resonance imaging (MRI) (DWI) and perfusion-weighted MRI (PWI) to evaluate the efficacy of thrombolysis in experimental embolic stroke using a plasminogen activator, reteplase. Reteplase (rPA) is an unglycosylated plasminogen activator with enhanced fibrinolytic potency. Right internal carotid arteries of 34 rabbits were embolized using aged heterologous thrombi. Baseline DWI and PWI scans 0.5 hours after embolization confirmed successful embolization among 32. Intravenous treatment with rPA (n=11; 1 mg/kg bolus), recombinant tissue plasminogen activator (rt-PA) (n=11; 6 mg/kg bolus over 1 hour), or placebo (n=10) commenced 1 hour after stroke induction. MRIs were performed at 1.75, 3, and 5 hours after embolization. Six hours after embolization, brains were harvested and examined for hemorrhage. Posttreatment areas of diffusion abnormality and perfusion delay were graded using both a semiquantitative scale and percent areas expressed as a ratio of the baseline values. Improved perfusion was seen among the rt-PA, and rPA-treated groups compared with placebo, using a semiquantitative scale (P<.01 rt-PA v controls, P<.05, rPA v controls). DWI scans, however, were not improved with thrombolysis. Cerebral hemorrhage was not increased with thrombolytic treatment, although the incidence of wound site hemorrhage was higher with either rPA or rt-PA. One fatal systemic hemorrhage was observed in each of the thrombolytic-treated groups. Cerebral perfusion was equally improved with either rt-PA or rPA without causing excess cerebral hemorrhage. An advantage of rPA is single-bolus dosing rather than continuous infusion. Use of rPA for stroke treatment should be further explored.
 ...
PMID:Thrombolysis with reteplase, an unglycosylated plasminogen activator variant, in experimental embolic stroke. 1789 78

Complete inferior vena cava thrombosis (IVC) in neonates is uncommon, but may cause significant morbidity. A 13-day-old neonate suffered IVC thrombosis secondary to antithrombin III deficiency, possibly contributed to by a mutation in the methyl tetrahydrofolate reductase gene. Catheter-directed thrombolysis (CDT) with recombinant tissue plasminogen activator (rt-PA, Alteplase) was used successfully to treat extensive venous thrombosis in this neonate without complications. We also review the literature on CDT for treatment of IVC thrombosis in critically ill neonates and infants.
 ...
PMID:Catheter-directed thrombolysis of inferior vena cava thrombosis in a 13-day-old neonate and review of literature. 1800 20

Thrombolytic therapy has been shown to reduce mortality after acute myocardial infarction. Great efforts have been undertaken in the past decade to develop more efficient thrombolytic regimens. Novel recombinant thrombolytic substances have been engineered. Reteplase, a deletion mutant of wild-type tissue plasminogen activator with a longer half-life, has been evaluated in clinical trials and is now available for clinical use. In the randomised Reteplase Angiographic Phase II International Dose-Finding (RAPID-1) trial, involving 606 patients with acute myocardial infarction, a double-bolus regimen of reteplase (10 + 10U given 30 minutes apart) achieved significantly higher patency rates at 90 minutes after initiation of thrombolytic therapy than a 10 + 5U double-bolus reteplase regimen, a 15U single bolus reteplase regimen, or a conventional alteplase regimen (100mg in 180 minutes). In the Reteplase versus Alteplase Patency Investigation During Acute Myocardial Infarction (RAPID-2) trial, the reteplase 10 + 10U double-bolus regimen was more effective with regard to patency at 60 and 90 minutes than accelerated alteplase (100mg in 90 minutes). The International Joint Efficacy Comparison of Thrombolytics (INJECT) trial showed that a double-bolus regimen of reteplase 10 + 10U was at least equivalent to streptokinase in terms of 35-day mortality rate. The third Global Utilization of Strategies to Open Occluded Coronary Arteries (GUSTO-III) trial resulted in similar 30-day mortality after therapy with double-bolus reteplase 10 + 10U (7.47%) or accelerated alteplase (7.24%). Hence, the higher early patency rates achieved with reteplase treatment did not translate into improved survival. Consequently, there is still some uncertainty as to whether or not these drugs are equivalent.
 ...
PMID:Recombinant plasminogen activators: a comparative review of the clinical pharmacology and therapeutic use of alteplase and reteplase. 1802 May 78


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>