Activase

Activase 550/20 mg Thrombolytic encymes lyophilized recombinant tPA Genentech... 

Substrate RuBP binds much more tightly to the inactive E form of rubisco (An = 20 nM) than to the active ECM form (A, for RuBP = 20 ixM). Thus, RuBP is also a potent inhibitor of rubisco activity. Release of RuBP from the active site of rubisco is mediated by rubisco activase. Rubisco activase is a regulatory protein it binds to A-form rubisco and, in an ATP-dependent reaction, promotes the release of RuBP. Rubisco then becomes activated by carbamylation and Mg binding. Rubisco activase itself is activated in an indirect manner by light. Thus, light is the ultimate activator of rubisco. 

As discussed in Section 22.7, illumination of chloroplasts leads to light-driven pumping of protons into the thylakoid lumen, which causes pH changes in both the stroma and the thylakoid lumen (Figure 22.27). The stromal pH rises, typically to pH 8. Because rubisco and rubisco activase are more active at pH 8, COg fixation is activated as stromal pH rises. Fructose-1,6-bisphosphatase, ribulose-5-phosphate kinase, and glyceraldehyde-3-phosphate dehydrogenase all have alkaline pH optima. Thus, their activities increase as a result of the light-induced pH increase in the stroma. 

The NINDS rt-PA smdy was divided into two parts. NINDS part I included 291 patients and NINDS part II included 333 patients. In both parts, acute ischemic stroke patients presenting within 3 hours of symptom onset were randomized to placebo versus treatment with the human rt-PA Alteplase (Activase). The dose was 0.9 mg/kg (maximum dose 90 mg), with 10% of the total dose given as a bolus and the remaining 90% infused over 60 minutes. Inclusion and exclusion criteria for both parts are listed in Table 3.2. These criteria are now the standard clinical criteria used to determine IV rt-PA eligibility in acute stroke patients. 

Alteplase (rt-PA Activase) is an IV thrombolytic (fibrinolytic) that was approved for acute stroke treatment in 1996 based on the results of the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trial.10 The current American Stroke Association guidelines include alteplase as the only Food and Drug Administration (FDA) approved acute treatment for ischemic stroke and strongly encourage early diagnosis and treatment of appropriate patients.11... 

Activase Alteplase, recombinant Genentech Acute myordial infarction, acute massive pulmonary embolism, ischemic stroke... 

Activase (tissue Lyophile for IV injection Stable up to 8 hr at room temp, after lOOmg vial 3.5g L-Arg, lg... 

Blood factors, anticoagulants and thrombolytics Activase, Advate, Benefix, Bioclate, Helixate/ Kogenate, Metalyse/TNKase, Novoseven, Recombinate, Refacto, Xigiris... 

Urokinase (Abbokinase) For PE, 4,400 international units/kg IV over 10 minutes followed by 4,400 international units/kg/hour for 12 to 24 hours. / Alteplase (Activase) For PE, 100 mg by IV infusion over 2 hours. 

Others Osteoporosis, asthma, cystic fibrosis, acute myocardial infarction, severe sepsis, psoriasis, non-Hodgkin s lymphoma Forteo, Xolair, Puhnozyme, Activase/TNKase, Xigris, Raptiva, Zevahn... 

Tissue plasminogen Thrombolytic activator (Activase, t-PA, Alteplase)... 

Both forms of t-PA and rt-PA have very short half-lives (about 3 min), and they are quickly removed from the organism, mainly by the liver. Therefore, they are used only by infusion methods. They can be prescribed for patients who cannot use streptokinase (for example, those patients that recently had a streptococcus infection). Synonyms of this drag are activase and others. 

Aheplase Recombinant [tPA] (Activase) [Plasminogen ActlVator/ThrombolytlC Enzyme] Uses AMI, PE, acute ischemic stroke, CV cath occlusion Action Thrombolytic binds fibrin in thrombus, initiates fibrinolysis Dose AMI 15 mg IV over 1-2 min, then 0.75 mg kg (max 50 mg) over 30 min, then 0.5 mg/kg over next 60 min (max 35 mg) (ECC 2005) Stroke 0.09 mg/kg IV over 1 min, then 0.81 mg/kg max 90 mg) inf over 60 min... 

FFeart disease, particularly clogged blood vessels, is also treated with recombinant products. Alteplase (Activase ), a human recombinant protein that breaks down fibrin, is used immediately after a stroke or heart attack to break down platelet-trapping clots in small blood vessels of the heart or brain and thus improve the patient s chances for recovery. Purified enzymes from bacteria are used for the same purposes. Abciximab (ReoPro ), a monoclonal antibody to... 

Genenteeh was founded in 1976 by scientist Herbert Boyer and the venture capitalist, Robert Swanson. Headquartered in San Francisco, it employs almost 5000 staff worldwide and has 10 protein-based products on the market. These include human growth hormones ( Nutropin , Chapter 8), the antibody-based products Herceptin and Rituxan (Chapter 10) and the thrombolytic agents Activase and TNKase (Chapter 9). The company also has 20 or so products in clinical trials. In 2001, it generated some US 2.2 billion in revenues, 24% of which it reinvested in R D. 

Activase has proved effective in the early treatment of patients with acute myocardial infarction (i.e. those treated within 12 h after the first symptoms occur). Significantly increased rates of patient survival (as measured 1 day and 30 days after the initial event), are noted when tPA is administered in favour of streptokinase, a standard therapy (see later). tPA has thus established itself as a first-line option in the management of acute myocardial infarction. A therapeutic dose of 90-100 mg (often administered by infusion over 90 min), results in a steady-state Activase concentration of 3-4mg/l during that period. The product is, however, cleared rapidly by the liver, displaying a serum half-life of approximately 3 min. As is the case for most thrombolytic agents, the most significant risk associated with tPA administration is the possible induction of severe haemorrhage. 

Activase (Alteplase, rh-tPA produced in CHO cells) Genentech Acute myocardial infarction 1987 (USA)... 

Powder for Infection 2 mg (Cathflo Activase), 50 mg (Activase), 100 mg (Activase). Indications and Dosages ... 

Some of the previously unavailable enzymes for therapeutic use include domase (Pulmozyme), imiglucerase (Cerezyme), asparaginase, tissue-type plasminogen activator (Activase), and related drugs (Retavase). Detailed information about these products and their clinical use is provided in Part II in the form of monographs. Information relevant to pharmacokinetics and molecular characteristics can be found in Appendixes I and II. 

Dosage form Activase is a sterile, lyophilized powder for intravenous administration after reconstitution with sterile water for injection. Each vial contains alteplase 50 or 100 mg. 

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