Tenecteplase Half-Life
Tenecteplase has a terminal phase half-life of 90 to 130 minutes after intravenous bolus administration, which is substantially longer than alteplase's half-life of approximately 2.4 minutes. 1, 2
Pharmacokinetic Profile
The FDA-approved drug label for tenecteplase (TNKase) specifies that after IV bolus administration, the terminal phase half-life ranges from 90 to 130 minutes in patients with ST-elevation myocardial infarction 1
This extended half-life is approximately 18 minutes in some literature sources, though the FDA label provides the more precise terminal elimination half-life of 90-130 minutes 3, 1
Tenecteplase exhibits biphasic disposition from plasma, with an initial volume of distribution at central compartment of 4.22 to 5.43 L (approximating plasma volume), and steady-state volume of distribution of 6.12 to 8.01 L 1
Clinical Significance of Extended Half-Life
The longer half-life compared to alteplase (which has a half-life of only ~2.4 minutes) permits single-bolus administration rather than the 1-hour infusion required for alteplase 4, 2
This single-bolus administration offers significant workflow advantages, particularly in centers considering endovascular therapy or patient transfer 4
The extended half-life results from tenecteplase being a genetically modified variant of alteplase with three key modifications: substitution of threonine 103 with asparagine, substitution of asparagine 117 with glutamine (both in the kringle 1 domain), and a tetra-alanine substitution at amino acids 296-299 in the protease domain 1
Metabolism and Clearance
Liver metabolism is the major clearance mechanism for tenecteplase 1
Mean plasma clearance ranges from 99 to 119 mL/min across the 30,40, and 50 mg doses, demonstrating linear pharmacokinetics 1
Total body weight explains 19% of the variability in plasma clearance and 11% of the variability in volume of distribution 1
Comparison with Other Thrombolytics
Tenecteplase has 14-fold greater fibrin specificity than alteplase and 80-fold greater resistance to inhibition by plasminogen activator inhibitor type 1 3
Other plasminogen activators like reteplase also have longer half-lives than alteplase, allowing for bolus administration, though tenecteplase remains distinct in its pharmacokinetic profile 5