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Identification
NameAprotinin
Accession NumberDB06692
Typebiotech
Groupsapproved, withdrawn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 The drug was temporarily withdrawn worldwide in 2007 after studies suggested that its use increased the risk of complications or death; after this was confirmed by follow-up studies, Trasylol was entirely and permanently withdrawn in May 2008, except – at least for the time being – for very restricted research use.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 structureNo structure small
Protein chemical formulaC284H432N84O79S7
Protein average weight6511.4390
Sequences
>Aprotinin (bovine pancreatic trypsin inhibitor)
RPDFCLEPPYTGPCKARIIRYFYNAKAGLCQTFVYGGCRAKRNNFKSAEDCMRTCGGA
Download FASTA Format
Synonyms
SynonymLanguageCode
bovine pancreatic trypsin inhibitorNot AvailableNot Available
BPTINot AvailableNot Available
IniprolNot AvailableNot Available
TrazininNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
TrasylolBayer
Brand mixtures
Brand NameIngredients
Tisseel Kit Vh 1.0Aprotinin (Bovine) + Calcium Chloride + Factor Xiii + Fibrinogen (Human) + Plasmafibronectin (Cig) + Plasminogen + Thrombin (Human) + Total Protein
Tisseel Kit Vh 2.0Aprotinin (Bovine) + Calcium Chloride + Factor Xiii + Fibrinogen (Human) + Plasmafibronectin (Cig) + Plasminogen + Thrombin (Human) + Total Protein
Tisseel Kit Vh 5.0Aprotinin (Bovine) + Calcium Chloride + Factor Xiii + Fibrinogen (Human) + Plasmafibronectin (Cig) + Plasminogen + Thrombin (Human) + Total Protein
Categories
CAS number9087-70-1
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentPeptides
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationFor 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.
PharmacodynamicsAprotinin 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 actionAprotinin 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.
Absorption100% (IV)
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Aprotinin is slowly degraded by lysosomal enzymes.

Route of eliminationFollowing 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 lifeFollowing 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.
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Aprotinin Action PathwayDrug actionSMP00288
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption Not Available Not Available
Blood Brain Barrier Not Available Not Available
Caco-2 permeable Not Available Not Available
P-glycoprotein substrate Not Available Not Available
P-glycoprotein inhibitor I Not Available Not Available
P-glycoprotein inhibitor II Not Available Not Available
Renal organic cation transporter Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 1A2 substrate Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 2C19 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 inhibitory promiscuity Not Available Not Available
Ames test Not Available Not Available
Carcinogenicity Not Available Not Available
Biodegradation Not Available Not Available
Rat acute toxicity Not Available Not applicable
hERG inhibition (predictor I) Not Available Not Available
hERG inhibition (predictor II) Not Available Not Available
Pharmacoeconomics
Manufacturers
  • Bayer healthcare pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
SolutionIntra-arterial
PricesNot Available
PatentsNot Available
Properties
Stateliquid
Experimental PropertiesNot Available
Spectra
SpectraNot Available
References
Synthesis Reference

Marion Steinbuch, Jacques Chabbat, Olivier Taby, “Process for preparation of activated protein C by immobilized aprotinin chromatography.” U.S. Patent US5198534, issued February, 1985.

US5198534
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
ResourceLink
PharmGKBPA448472
Drug Product Database2186845
RxListhttp://www.rxlist.com/trasylol-drug.htm
Drugs.comhttp://www.drugs.com/cdi/aprotinin.html
WikipediaAprotinin
ATC CodesB02AB01
AHFS Codes
  • 20:28.16
PDB EntriesNot Available
FDA labelshow(108 KB)
MSDSshow(19.5 KB)
Interactions
Drug Interactions
Drug
CaptoprilIn 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.
HeparinAprotinin, 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.
TenecteplaseAprotonin may antagonize the effect of Tenecteplase. Monitor for decreased effects of Tenecteplase.
UrokinaseAprotonin may antagonize the effect of Urokinase. Monitor for decreased effects of Urokinase.
Food InteractionsNot Available

1. Trypsin-1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Trypsin-1 P07477 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Chymotrypsinogen B P17538 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Plasminogen P00747 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Kallikrein-1 P06870 Details

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 13, 2013 11:15