Alteplase and tenecteplase: applications in the peripheral circulation.
Alteplase (t-PA), a recombinant analogue of human tissue plasminogen activator, became the first genetically engineered thrombolytic approved by the Food and Drug Administration in 1987 for acute myocardial infarction (AMI). In addition to AMI, alteplase is currently approved for the treatment of acute ischemic stroke and pulmonary embolism, and we anticipate approval for catheter clearance in late 2001 in a 2-mg vial configuration. With the withdrawal of human neonatal kidney cell-derived urokinase, alteplase has become an alternative agent in peripheral vascular applications. Because few interventionalists had prior experience with the handling and dosage of alteplase, the Advisory Panel to the Society of Cardiovascular and Interventional Radiology established practice guidelines for use in noncoronary applications. Emerging clinical experience with contemporary dosing regimens shows a safety and efficacy profile similar to urokinase but with significantly reduced drug costs. Tenecteplase (TNK) is a genetically modified version of alteplase. TNK is the only plasminogen activator available that has shown a significantly enhanced safety profile versus alteplase in AMI. Approved for a 5-second, single-bolus injection in AMI, TNK possesses a longer half-life, increased resistance to plasminogen activator inhibitor, and improved fibrin specificity compared with alteplase. Because of its enhanced safety profile, TNK may be a desirable agent for peripheral vascular applications. Initial clinical studies with TNK in acute arterial and venous disease are ongoing. This article outlines the Advisory Panel guidelines for using alteplase and highlights features of tenecteplase.
Semba
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CP
Cardiovascular Clinical Research, Genentech Inc., MS 59, 1 DNA Way, South San Francisco, CA 94080-4990, USA.
Sugimoto
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K
Razavi
M K
MK
D001775:Blood Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000592:standards / Q000627:therapeutic use*; D006801:Humans; D000077785:Tenecteplase; D015912:Thrombolytic Therapy / Q000592:standards; D010959:Tissue Plasminogen Activator / Q000494:pharmacology* / Q000592:standards / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology / Q000592:standards / Q000627:therapeutic use; D014654:Vascular Patency / Q000187:drug effects
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D000077785:Tenecteplase