Tenecteplase: A Comprehensive Pharmacological and Clinical Review

1. Introduction to Tenecteplase

Tenecteplase is a third-generation thrombolytic agent, representing a significant advancement in the pharmacotherapy of acute thrombotic events. It is a genetically engineered variant of human tissue plasminogen activator (tPA), a naturally occurring serine protease integral to the endogenous fibrinolytic system.[1] The primary clinical utility of Tenecteplase lies in the emergency management of conditions where rapid dissolution of blood clots is critical, most notably in acute ST-segment elevation myocardial infarction (STEMI) and, following more recent investigations and regulatory approvals, in acute ischemic stroke (AIS).[1]

The development of Tenecteplase was driven by the objective to improve upon the characteristics of earlier generation tPAs, particularly alteplase. This was achieved through targeted modifications to the tPA protein structure, resulting in an agent with enhanced fibrin specificity, a greater resistance to inactivation by its principal physiological inhibitor, plasminogen activator inhibitor-1 (PAI-1), and a considerably longer plasma half-life.[2] These refined pharmacological properties confer a major practical advantage: the ability to administer Tenecteplase as a single, weight-adjusted intravenous (IV) bolus. This simplified administration contrasts with the more complex bolus and infusion regimens required for older agents like alteplase.[2]