Tenecteplase

Last updated

Tenecteplase
Clinical data
Trade names Tnkase
AHFS/Drugs.com Monograph
Drug class Tissue plasminogen activator
ATC code
Legal status
Legal status
Pharmacokinetic data
Excretion Liver
Identifiers
  • Human tissue plasminogen activator
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
Formula C2561H3919N747O781S40
Molar mass 58951.37 g·mol−1
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Tenecteplase, sold under the brand names Tnkase among others, is an enzyme used as a thrombolytic drug.

Contents

Tenecteplase is a tissue plasminogen activator (tPA) produced by recombinant DNA technology using an established mammalian cell line (Chinese hamster ovary cells). [1] Tenecteplase is a 527 amino acid glycoprotein developed by introducing the following modifications to the complementary DNA for natural human tPA: a substitution of threonine 103 with asparagine, and a substitution of asparagine 117 with glutamine, both within the kringle 1 domain, and a tetra-alanine substitution at amino acids 296–299 in the protease domain.

Tenecteplase is a recombinant fibrin-specific plasminogen activator that is derived from native t-PA by modifications at three sites of the protein structure. It binds to the fibrin component of the thrombus (blood clot) and selectively converts thrombus-bound plasminogen to plasmin, which degrades the fibrin matrix of the thrombus. Tenecteplase has a higher fibrin specificity and greater resistance to inactivation by its endogenous inhibitor (PAI-1) compared to native t-PA.

Tenecteplase was approved for medical use in the United States in June 2000. [1] [3]

Medical uses

Tenecteplase is indicated to reduce the risk of death associated with acute ST elevation myocardial infarction and acute ischemic stroke. [1]

Pharmacokinetics

Distribution: approximates plasma volume

Metabolism: Primarily hepatic

Half-life elimination: Biphasic: Initial: 20–24 minutes; Terminal: 90–130 minutes

Excretion: Clearance: Plasma: 99–119 mL/minute

Research

Researchers at Newcastle University in Australia say they have had a significant breakthrough in treating stroke patients using the commonly used drug. [4] The findings were published in the New England Medical Journal. Though safety has been established through previous clinical trials, there is ongoing debate about whether this is an effective treatment for ischemic stroke, and significant ongoing discussion between emergency physicians, neurologists and pharmacists about whether this treatment should be used for that indication.

The American Heart Association/American Stroke Association 2019 update to the 2018 guidelines for the Early Management of Acute Ischemic Stroke supports considering tenecteplase over alteplase in patients without contraindication to intravenous thrombolytics. [5]

References

  1. 1 2 3 4 "Tnkase- tenecteplase kit". DailyMed. 18 December 2024. Retrieved 28 February 2025.
  2. "Tnkase- tenecteplase kit". DailyMed. 10 January 2024. Retrieved 28 February 2025.
  3. "Tenecteplase Product Approval Information". U.S. Food and Drug Administration (FDA). 3 November 2008. Archived from the original on 19 January 2009. Retrieved 28 February 2025.
  4. Parsons M, Spratt N, Bivard A, Campbell B, Chung K, Miteff F, et al. (March 2012). "A randomized trial of tenecteplase versus alteplase for acute ischemic stroke". The New England Journal of Medicine. 366 (12): 1099–1107. doi:10.1056/NEJMoa1109842. hdl: 1959.13/1039697 . PMID   22435369.{{cite journal}}: CS1 maint: overridden setting (link)
  5. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. (December 2019). "Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association". Stroke. 50 (12): e344 –e418. doi: 10.1161/str.0000000000000211 . PMID   31662037. S2CID   204973899.{{cite journal}}: CS1 maint: overridden setting (link)

Further reading