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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GroupsApproved, Withdrawn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 The drug was temporarily withdrawn worldwide in 2007 after studies suggested that its use increased the risk of complications or death; after this was confirmed by follow-up studies, Trasylol was entirely and permanently withdrawn in May 2008, except – at least for the time being – for very restricted research use.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 structureDb06692
Protein chemical formulaC284H432N84O79S7
Protein average weight6511.439 Da
Sequences
>Aprotinin (bovine pancreatic trypsin inhibitor)
RPDFCLEPPYTGPCKARIIRYFYNAKAGLCQTFVYGGCRAKRNNFKSAEDCMRTCGGA
Download FASTA Format
Synonyms
bovine pancreatic trypsin inhibitor
BPTI
Iniprol
Trazinin
External Identifiers
  • Bayer A 128
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Trasylolsolution10000 unitintravenousNordic Group B.V.1997-12-15Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Trasylol Inj 10000 Kiu/mlliquid100000 unitintravenousMiles Canada Inc. Pharmaceutical Division1981-12-311998-09-25Canada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number9087-70-1
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Solutionintravenous10000 unit
Liquidintravenous100000 unit
PricesNot Available
PatentsNot Available
Properties
StateLiquid
Experimental Properties
PropertyValueSource
melting point>100 °CNot 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 References
  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
ATC CodesB02AB01
AHFS Codes
  • 20:28.16
PDB Entries
FDA labelDownload (108 KB)
MSDSDownload (19.5 KB)
Interactions
Drug Interactions
Drug
AlteplaseThe therapeutic efficacy of Alteplase can be decreased when used in combination with Aprotinin.
AnistreplaseThe therapeutic efficacy of Anistreplase can be decreased when used in combination with Aprotinin.
BenazeprilAprotinin may decrease the antihypertensive activities of Benazepril.
CaptoprilAprotinin may decrease the antihypertensive activities of Captopril.
CilazaprilAprotinin may decrease the antihypertensive activities of Cilazapril.
EnalaprilAprotinin may decrease the antihypertensive activities of Enalapril.
EnalaprilatAprotinin may decrease the antihypertensive activities of Enalaprilat.
FosinoprilAprotinin may decrease the antihypertensive activities of Fosinopril.
LisinoprilAprotinin may decrease the antihypertensive activities of Lisinopril.
MoexiprilAprotinin may decrease the antihypertensive activities of Moexipril.
PerindoprilAprotinin may decrease the antihypertensive activities of Perindopril.
QuinaprilAprotinin may decrease the antihypertensive activities of Quinapril.
RamiprilAprotinin may decrease the antihypertensive activities of Ramipril.
ReteplaseThe therapeutic efficacy of Reteplase can be decreased when used in combination with Aprotinin.
RidogrelThe therapeutic efficacy of Ridogrel can be decreased when used in combination with Aprotinin.
StreptokinaseThe therapeutic efficacy of Streptokinase can be decreased when used in combination with Aprotinin.
TenecteplaseThe therapeutic efficacy of Tenecteplase can be decreased when used in combination with Aprotinin.
TrandolaprilAprotinin may decrease the antihypertensive activities of Trandolapril.
UrokinaseThe therapeutic efficacy of Urokinase can be decreased when used in combination with Aprotinin.
Food InteractionsNot Available

Targets

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

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Drug created on February 12, 2009 09:44 / Updated on August 07, 2014 11:13