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Identification
Name Aprotinin
Accession Number DB06692
Type biotech
Groups approved, withdrawn
Description

Aprotinin, also known as bovine pancreatic trypsin inhibitor, BPTI (Trasylol, Bayer) is a protein, that is used as medication administered by injection to reduce bleeding during complex surgery, such as heart and liver surgery. Its main effect is the slowing down of fibrinolysis, the process that leads to the breakdown of blood clots. The aim in its use is to decrease the need for blood transfusions during surgery, as well as end-organ damage due to hypotension (low blood pressure) as a result of marked blood loss. The drug was temporarily withdrawn worldwide in 2007 after studies suggested that its use increased the risk of complications or death; after this was confirmed by follow-up studies, Trasylol was entirely and permanently withdrawn in May 2008, except – at least for the time being – for very restricted research use. [Wikipedia]
Protein structure No_structure_small
Protein chemical formula C284H432N84O79S7
Protein average weight 6511.4390
Sequences 
>Aprotinin (bovine pancreatic trypsin inhibitor)
RPDFCLEPPYTGPCKARIIRYFYNAKAGLCQTFVYGGCRAKRNNFKSAEDCMRTCGGA

FASTA
Synonyms
Bayer A 128
bovine pancreatic trypsin inhibitor
BPTI
Iniprol
Trazinin
Salts Not Available
Brand names
Name Company
Trasylol Bayer
Brand mixtures
Brand Name Ingredients
Tisseel Kit Vh 1.0 Aprotinin (Bovine) + Calcium Chloride + Factor Xiii + Fibrinogen (Human) + Plasmafibronectin (Cig) + Plasminogen + Thrombin (Human) + Total Protein
Tisseel Kit Vh 2.0 Aprotinin (Bovine) + Calcium Chloride + Factor Xiii + Fibrinogen (Human) + Plasmafibronectin (Cig) + Plasminogen + Thrombin (Human) + Total Protein
Tisseel Kit Vh 5.0 Aprotinin (Bovine) + Calcium Chloride + Factor Xiii + Fibrinogen (Human) + Plasmafibronectin (Cig) + Plasminogen + Thrombin (Human) + Total Protein
Categories
  • Antifibrinolytic Agents
CAS number 9087-70-1
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication For prophylactic use to reduce perioperative blood loss and the need for blood transfusion in patients undergoing cardiopulmonary bypass in the course of coronary artery bypass graft surgery who are at an increased risk for blood loss and blood transfusion.
Pharmacodynamics Aprotinin is a broad spectrum protease inhibitor which modulates the systemic inflammatory response (SIR) associated with cardiopulmonary bypass (CPB) surgery. SIR results in the interrelated activation of the hemostatic, fibrinolytic, cellular and humoral inflammatory systems. Aprotinin, through its inhibition of multiple mediators [e.g., kallikrein, plasmin] results in the attenuation of inflammatory responses, fibrinolysis, and thrombin generation. Aprotinin inhibits pro-inflammatory cytokine release and maintains glycoprotein homeostasis. In platelets, aprotinin reduces glycoprotein loss (e.g., GpIb, GpIIb/IIIa), while in granulocytes it prevents the expression of pro-inflammatory adhesive glycoproteins (e.g., CD11b). The effects of aprotinin use in CPB involves a reduction in inflammatory response which translates into a decreased need for allogeneic blood transfusions, reduced bleeding, and decreased mediastinal re-exploration for bleeding.
Mechanism of action Aprotinin inhibits several serine proteases, specifically trypsin, chymotrypsin and plasmin at a concentration of about 125,000 IU/ml, and kallikrein at 300,000 IU/ml. Its action on kallikrein leads to the inhibition of the formation of factor XIIa. As a result, both the intrinsic pathway of coagulation and fibrinolysis are inhibited. Its action on plasmin independently slows fibrinolysis.
Absorption 100% (IV)
Volume of distribution Not Available
Protein binding Not Available
Metabolism Aprotinin is slowly degraded by lysosomal enzymes.
Route of elimination Following a single IV dose of radiolabelled aprotinin, approximately 25-40% of the radioactivity is excreted in the urine over 48 hours. After a 30 minute infusion of 1 million KIU, about 2% is excreted as unchanged drug. After a larger dose of 2 million KIU infused over 30 minutes, urinary excretion of unchanged aprotinin accounts for approximately 9% of the dose.
Half life Following this distribution phase, a plasma half-life of about 150 minutes is observed. At later time points, (i.e., beyond 5 hours after dosing) there is a terminal elimination phase with a half-life of about 10 hours.
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00288 Aprotinin Pathway SMP00288
Pharmacoeconomics
Manufacturers
  • Bayer healthcare pharmaceuticals inc
Packagers
Dosage forms
Form Route Strength
Solution Intra-arterial
Prices Not Available
Patents Not Available
Properties
State liquid
Experimental Properties Not Available
References
Synthesis Reference Not Available
General Reference
  1. Mahdy AM, Webster NR: Perioperative systemic haemostatic agents. Br J Anaesth. 2004 Dec;93(6):842-58. Epub 2004 Jul 26. Pubmed
External Links
Resource Link
PharmGKB PA448472 Link_out
Drug Product Database 2186845 Link_out
RxList http://www.rxlist.com/trasylol-drug.htm Link_out
Drugs.com http://www.drugs.com/cdi/aprotinin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Aprotinin Link_out
ATC Codes
  • B02AB01
AHFS Codes
  • 20:28.16
PDB Entries Not Available
FDA label show (108 KB)
MSDS show (19.5 KB)
Interactions
Drug Interactions
Drug Interaction
Captopril In study of nine patients with untreated hypertension, aprotinin infused intravenously in a dose of 2 million KIU over two hours blocked the acute hypotensive effect of 100mg of captopril.
Heparin Aprotinin, in the presence of heparin, has been found to prolong the activated clotting time (ACT) as measured by a celite surface activation method. The kaolin activated clotting time appears to be much less affected.
Tenecteplase Aprotonin may antagonize the effect of Tenecteplase. Monitor for decreased effects of Tenecteplase.
Urokinase Aprotonin may antagonize the effect of Urokinase. Monitor for decreased effects of Urokinase.
Food Interactions Not Available
Targets

1. Trypsin-1

Pharmacological action: unknown

Preferential cleavage:Arg-|-Xaa, Lys-|-Xaa

Organism class: human
UniProt ID: P07477 Link_out
Gene: PRSS1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mahdy AM, Webster NR: Perioperative systemic haemostatic agents. Br J Anaesth. 2004 Dec;93(6):842-58. Epub 2004 Jul 26. Pubmed

2. Chymotrypsinogen B

Pharmacological action: unknown

Preferential cleavage:Tyr-|-Xaa, Trp-|-Xaa, Phe-|-Xaa, Leu-|-Xaa

Organism class: human
UniProt ID: P17538 Link_out
Gene: CTRB1 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mahdy AM, Webster NR: Perioperative systemic haemostatic agents. Br J Anaesth. 2004 Dec;93(6):842-58. Epub 2004 Jul 26. Pubmed

3. Plasminogen

Pharmacological action: unknown

Angiostatin is an angiogenesis inhibitor that blocks neovascularization and growth of experimental primary and metastatic tumors in vivo

Organism class: human
UniProt ID: P00747 Link_out
Gene: PLG Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mahdy AM, Webster NR: Perioperative systemic haemostatic agents. Br J Anaesth. 2004 Dec;93(6):842-58. Epub 2004 Jul 26. Pubmed

4. Kallikrein-1

Pharmacological action: unknown

Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin

Organism class: human
UniProt ID: P06870 Link_out
Gene: KLK1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mahdy AM, Webster NR: Perioperative systemic haemostatic agents. Br J Anaesth. 2004 Dec;93(6):842-58. Epub 2004 Jul 26. Pubmed
Comments
Drug created on February 12, 2009 09:44 / Updated on September 29, 2010 14:35