Tenecteplase

Tenecteplase

Clinical data
Trade names	Tnkase
AHFS/Drugs.com	Monograph
Drug class	Tissue plasminogen activator
ATC code	B01AD11 ( WHO )
Legal status
Legal status	US: ℞-only [1] [2] In general: ℞ (Prescription only)
Pharmacokinetic data
Excretion	Liver
Identifiers
IUPAC name Human tissue plasminogen activator
CAS Number	191588-94-0  Y
DrugBank	DB00031  Y
ChemSpider	none
UNII	WGD229O42W
KEGG	D02837  Y
Chemical and physical data
Formula	C2561H3919N747O781S40
Molar mass	58951.37 g·mol−1
NY  (what is this?)    (verify)

Tenecteplase, sold under the brand names Tnkase among others, is an enzyme used as a thrombolytic drug.

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

Gallery

• 
  Here is TNK-tPA. It is very similar to t-PA, but the glycosylation occurring in Kringle 1 is manipulated. The mutation T103N means that glycosylation occurs at that point. The mutation N117Q means that the high mannose sugar residue is absent at that point.
• 
  In human t-PA, the amino acids at position 296–299 are lysine, histidine, and two arginines.
• 
  In TNK-tPA, these amino acids have been replaced by four alanines. This mutation is responsible for increased resistance to PAI-1.

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. "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.
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.

Further reading

• Gurbel PA, Hayes K, Bliden KP, Yoho J, Tantry US (January 2005). "The platelet-related effects of tenecteplase versus alteplase versus reteplase". Blood Coagulation & Fibrinolysis. 16 (1): 1–7. doi:10.1097/00001721-200501000-00001. PMID   15650539. S2CID   44664652.
• Melzer C, Richter C, Rogalla P, Borges AC, Theres H, Baumann G, et al. (August 2004). "Tenecteplase for the treatment of massive and submassive pulmonary embolism". Journal of Thrombosis and Thrombolysis. 18 (1): 47–50. doi:10.1007/s11239-004-0174-z. PMID   15744554. S2CID   10947258.
• Ohman EM, Van de Werf F, Antman EM, Califf RM, de Lemos JA, Gibson CM, et al. (July 2005). "Tenecteplase and tirofiban in ST-segment elevation acute myocardial infarction: results of a randomized trial". American Heart Journal. 150 (1): 79–88. doi:10.1016/j.ahj.2005.01.007. PMID   16084152.
• De Luca G, Suryapranata H, Chiariello M (December 2005). "Tenecteplase followed by immediate angioplasty is more effective than tenecteplase alone for people with STEMI. Commentary". Evidence-Based Cardiovascular Medicine. 9 (4): 284–287. doi:10.1016/j.ebcm.2005.09.021. PMID   16380055.
• "Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI): randomised trial". Lancet. 367 (9510): 569–578. February 2006. doi:10.1016/S0140-6736(06)68147-6. PMID   16488800. S2CID   23972378.
• Bozeman WP, Kleiner DM, Ferguson KL (June 2006). "Empiric tenecteplase is associated with increased return of spontaneous circulation and short term survival in cardiac arrest patients unresponsive to standard interventions". Resuscitation. 69 (3): 399–406. doi:10.1016/j.resuscitation.2005.09.027. PMID   16563599.
• Hull JE, Hull MK, Urso JA, Park HA (April 2006). "Tenecteplase in acute lower-leg ischemia: efficacy, dose, and adverse events". Journal of Vascular and Interventional Radiology. 17 (4): 629–636. doi:10.1097/01.RVI.0000202751.74625.79. PMID   16614145.
• 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.