Tenecteplase

Tenecteplase, sold under the brand name Tnkase among others, is an enzyme used as a thrombolytic drug.^[1]

Tenecteplase

Clinical data
Trade names	Tnkase
AHFS/Drugs.com	Monograph
MedlinePlus	a625007
License data	US DailyMed: Tenecteplase
Routes of administration	Intravenous
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 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.^[1]

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][4]

Pharmacokinetics

Distribution: approximates plasma volume

Metabolism: Primarily liver

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  In TNK-tPA, these amino acids have been replaced by four alanines.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.^[5] 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.^[6]