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Identification
NameAprotinin
Accession NumberDB06692
TypeBiotech
GroupsApproved, Withdrawn
DescriptionAprotinin, 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 The drug was temporarily withdrawn worldwide in 2007 after studies suggested that its use increased the risk of complications or death; after this was confirmed by follow-up studies, Trasylol was entirely and permanently withdrawn in May 2008, except - at least for the time being - for very restricted research use.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
Related Articles
Protein chemical formulaC284H432N84O79S7
Protein average weight6511.439 Da
Sequences
>Aprotinin (bovine pancreatic trypsin inhibitor)
RPDFCLEPPYTGPCKARIIRYFYNAKAGLCQTFVYGGCRAKRNNFKSAEDCMRTCGGA
Download FASTA Format
Synonyms
Aprotinin (bovine)
Aprotinin Biosynthetic
Aprotinin Bovine
Aprotinin Concentrated Solution
Bovine Aprotinin
Bovine Pancreatic Trypsin Inhibitor
BPTI
Fibrinolysis Inhibitor
Trypsin Inhibitor, Pancreatic Basic
External Identifiers
  • 232-994-9
  • Bayer A 128
  • Bayer-A-128
  • Riker-52G
  • RP-9921
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Trasylolsolution10000 unitintravenousNordic Group B.V.1997-12-15Not applicableCanada
Trasylol Inj 10000 Kiu/mlliquid100000 unitintravenousMiles Canada Inc. Pharmaceutical Division1981-12-311998-09-25Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII04XPW8C0FL
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.
Related Articles
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
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:15277296 ]
External Links
ATC CodesB02AB01
AHFS Codes
  • 20:28.16
PDB Entries
FDA labelDownload (108 KB)
MSDSDownload (19.5 KB)
Interactions
Drug Interactions
Drug
AbacavirThe serum concentration of Abacavir can be decreased when it is combined with Aprotinin.
AbciximabThe therapeutic efficacy of Abciximab can be decreased when used in combination with Aprotinin.
AcenocoumarolThe therapeutic efficacy of Acenocoumarol can be decreased when used in combination with Aprotinin.
Acetylsalicylic acidThe therapeutic efficacy of Acetylsalicylic acid can be decreased when used in combination with Aprotinin.
AlfuzosinThe serum concentration of Alfuzosin can be increased when it is combined with Aprotinin.
AlprazolamThe serum concentration of Alprazolam can be increased when it is combined with Aprotinin.
AlteplaseThe therapeutic efficacy of Alteplase can be decreased when used in combination with Aprotinin.
ALX-0081The therapeutic efficacy of ALX-0081 can be decreased when used in combination with Aprotinin.
AmineptineThe serum concentration of Amineptine can be increased when it is combined with Aprotinin.
AminophyllineThe serum concentration of Aminophylline can be decreased when it is combined with Aprotinin.
AmitriptylineThe serum concentration of Amitriptyline can be increased when it is combined with Aprotinin.
AnagrelideThe therapeutic efficacy of Anagrelide can be decreased when used in combination with Aprotinin.
AncrodThe therapeutic efficacy of Ancrod can be decreased when used in combination with Aprotinin.
AnistreplaseThe therapeutic efficacy of Anistreplase can be decreased when used in combination with Aprotinin.
ApixabanThe therapeutic efficacy of Apixaban can be decreased when used in combination with Aprotinin.
ArdeparinThe therapeutic efficacy of Ardeparin can be decreased when used in combination with Aprotinin.
ArgatrobanThe therapeutic efficacy of Argatroban can be decreased when used in combination with Aprotinin.
AstaxanthinThe therapeutic efficacy of Astaxanthin can be decreased when used in combination with Aprotinin.
AtorvastatinThe serum concentration of Atorvastatin can be increased when it is combined with Aprotinin.
BatroxobinThe therapeutic efficacy of Batroxobin can be decreased when used in combination with Aprotinin.
BemiparinThe therapeutic efficacy of Bemiparin can be decreased when used in combination with Aprotinin.
BenazeprilAprotinin may decrease the antihypertensive activities of Benazepril.
BeraprostThe therapeutic efficacy of Beraprost can be decreased when used in combination with Aprotinin.
BivalirudinThe therapeutic efficacy of Bivalirudin can be decreased when used in combination with Aprotinin.
BoceprevirThe serum concentration of Aprotinin can be decreased when it is combined with Boceprevir.
BromocriptineThe serum concentration of Bromocriptine can be increased when it is combined with Aprotinin.
CabergolineThe serum concentration of Cabergoline can be increased when it is combined with Aprotinin.
CandoxatrilAprotinin may decrease the antihypertensive activities of Candoxatril.
CangrelorThe therapeutic efficacy of Cangrelor can be decreased when used in combination with Aprotinin.
CaptoprilAprotinin may decrease the antihypertensive activities of Captopril.
CarbamazepineThe metabolism of Aprotinin can be increased when combined with Carbamazepine.
CilazaprilAprotinin may decrease the antihypertensive activities of Cilazapril.
CilostazolThe therapeutic efficacy of Cilostazol can be decreased when used in combination with Aprotinin.
CisaprideThe serum concentration of Cisapride can be increased when it is combined with Aprotinin.
ClarithromycinThe therapeutic efficacy of Clarithromycin can be decreased when used in combination with Aprotinin.
ClomipramineThe serum concentration of Clomipramine can be increased when it is combined with Aprotinin.
ClopidogrelThe therapeutic efficacy of Clopidogrel can be decreased when used in combination with Aprotinin.
CyclobenzaprineThe serum concentration of Cyclobenzaprine can be increased when it is combined with Aprotinin.
CyclophosphamideThe risk or severity of adverse effects can be increased when Aprotinin is combined with Cyclophosphamide.
CyclosporineThe serum concentration of Cyclosporine can be increased when it is combined with Aprotinin.
Dabigatran etexilateThe therapeutic efficacy of Dabigatran etexilate can be decreased when used in combination with Aprotinin.
DalteparinThe therapeutic efficacy of Dalteparin can be decreased when used in combination with Aprotinin.
DanaparoidThe therapeutic efficacy of Danaparoid can be decreased when used in combination with Aprotinin.
DefibrotideThe therapeutic efficacy of Defibrotide can be decreased when used in combination with Aprotinin.
DelavirdineThe serum concentration of Delavirdine can be decreased when it is combined with Aprotinin.
DesipramineThe serum concentration of Desipramine can be increased when it is combined with Aprotinin.
DesirudinThe therapeutic efficacy of Desirudin can be decreased when used in combination with Aprotinin.
DesmoteplaseThe therapeutic efficacy of Desmoteplase can be decreased when used in combination with Aprotinin.
DicoumarolThe therapeutic efficacy of Dicoumarol can be decreased when used in combination with Aprotinin.
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Aprotinin.
DihydroergotamineThe serum concentration of Dihydroergotamine can be increased when it is combined with Aprotinin.
DipyridamoleThe therapeutic efficacy of Dipyridamole can be decreased when used in combination with Aprotinin.
DitazoleThe therapeutic efficacy of Ditazole can be decreased when used in combination with Aprotinin.
DosulepinThe serum concentration of Dosulepin can be increased when it is combined with Aprotinin.
DoxepinThe serum concentration of Doxepin can be increased when it is combined with Aprotinin.
Drotrecogin alfaThe therapeutic efficacy of Drotrecogin alfa can be decreased when used in combination with Aprotinin.
DyphyllineThe serum concentration of Dyphylline can be decreased when it is combined with Aprotinin.
EnalaprilAprotinin may decrease the antihypertensive activities of Enalapril.
EnalaprilatAprotinin may decrease the antihypertensive activities of Enalaprilat.
EnfuvirtideThe serum concentration of Enfuvirtide can be increased when it is combined with Aprotinin.
EnoxaparinThe therapeutic efficacy of Enoxaparin can be decreased when used in combination with Aprotinin.
EpoprostenolThe therapeutic efficacy of Epoprostenol can be decreased when used in combination with Aprotinin.
EptifibatideThe therapeutic efficacy of Eptifibatide can be decreased when used in combination with Aprotinin.
Ergoloid mesylateThe serum concentration of Ergoloid mesylate can be increased when it is combined with Aprotinin.
ErgonovineThe serum concentration of Ergonovine can be increased when it is combined with Aprotinin.
ErgotamineThe serum concentration of Ergotamine can be increased when it is combined with Aprotinin.
EsmirtazapineThe serum concentration of Esmirtazapine can be increased when it is combined with Aprotinin.
Ethyl biscoumacetateThe therapeutic efficacy of Ethyl biscoumacetate can be decreased when used in combination with Aprotinin.
EtravirineThe serum concentration of Etravirine can be decreased when it is combined with Aprotinin.
Fibrinogen Concentrate (Human)The risk or severity of adverse effects can be increased when Aprotinin is combined with Fibrinogen Concentrate (Human).
FibrinolysinThe therapeutic efficacy of Fibrinolysin can be decreased when used in combination with Aprotinin.
FosinoprilAprotinin may decrease the antihypertensive activities of Fosinopril.
GarlicThe serum concentration of Aprotinin can be decreased when it is combined with Garlic.
HeparinThe therapeutic efficacy of Heparin can be decreased when used in combination with Aprotinin.
IloprostThe therapeutic efficacy of Iloprost can be decreased when used in combination with Aprotinin.
ImipramineThe serum concentration of Imipramine can be increased when it is combined with Aprotinin.
LepirudinThe therapeutic efficacy of Lepirudin can be decreased when used in combination with Aprotinin.
LisinoprilAprotinin may decrease the antihypertensive activities of Lisinopril.
LovastatinThe serum concentration of Lovastatin can be increased when it is combined with Aprotinin.
MidazolamThe serum concentration of Midazolam can be increased when it is combined with Aprotinin.
MirtazapineThe serum concentration of Mirtazapine can be increased when it is combined with Aprotinin.
MoexiprilAprotinin may decrease the antihypertensive activities of Moexipril.
NadroparinThe therapeutic efficacy of Nadroparin can be decreased when used in combination with Aprotinin.
NCX 4016The therapeutic efficacy of NCX 4016 can be decreased when used in combination with Aprotinin.
NefazodoneThe serum concentration of Nefazodone can be increased when it is combined with Aprotinin.
NortriptylineThe serum concentration of Nortriptyline can be increased when it is combined with Aprotinin.
OmapatrilatAprotinin may decrease the antihypertensive activities of Omapatrilat.
ParnaparinThe therapeutic efficacy of Parnaparin can be decreased when used in combination with Aprotinin.
PerindoprilAprotinin may decrease the antihypertensive activities of Perindopril.
PethidineThe risk or severity of adverse effects can be increased when Aprotinin is combined with Pethidine.
PhenindioneThe therapeutic efficacy of Phenindione can be decreased when used in combination with Aprotinin.
PhenprocoumonThe therapeutic efficacy of Phenprocoumon can be decreased when used in combination with Aprotinin.
PimozideThe serum concentration of Pimozide can be increased when it is combined with Aprotinin.
PlasminThe therapeutic efficacy of Plasmin can be decreased when used in combination with Aprotinin.
PrasugrelThe therapeutic efficacy of Prasugrel can be decreased when used in combination with Aprotinin.
Protein CThe therapeutic efficacy of Protein C can be decreased when used in combination with Aprotinin.
ProtriptylineThe serum concentration of Protriptyline can be increased when it is combined with Aprotinin.
QuinaprilAprotinin may decrease the antihypertensive activities of Quinapril.
RamiprilAprotinin may decrease the antihypertensive activities of Ramipril.
RescinnamineAprotinin may decrease the antihypertensive activities of Rescinnamine.
ReteplaseThe therapeutic efficacy of Reteplase can be decreased when used in combination with Aprotinin.
ReviparinThe therapeutic efficacy of Reviparin can be decreased when used in combination with Aprotinin.
RiociguatThe serum concentration of Riociguat can be increased when it is combined with Aprotinin.
RivaroxabanThe therapeutic efficacy of Rivaroxaban can be decreased when used in combination with Aprotinin.
RosiglitazoneThe therapeutic efficacy of Rosiglitazone can be decreased when used in combination with Aprotinin.
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Aprotinin.
SelexipagThe therapeutic efficacy of Selexipag can be decreased when used in combination with Aprotinin.
SildenafilThe serum concentration of Sildenafil can be increased when it is combined with Aprotinin.
SimeprevirThe serum concentration of Simeprevir can be increased when it is combined with Aprotinin.
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Aprotinin.
SpiraprilAprotinin may decrease the antihypertensive activities of Spirapril.
St. John's WortThe metabolism of Aprotinin can be increased when combined with St. John's Wort.
StreptokinaseThe therapeutic efficacy of Streptokinase can be decreased when used in combination with Aprotinin.
SulodexideThe therapeutic efficacy of Sulodexide can be decreased when used in combination with Aprotinin.
TacrolimusThe metabolism of Tacrolimus can be decreased when combined with Aprotinin.
TemocaprilAprotinin may decrease the antihypertensive activities of Temocapril.
TemsirolimusThe risk or severity of adverse effects can be increased when Aprotinin is combined with Temsirolimus.
TenecteplaseThe therapeutic efficacy of Tenecteplase can be decreased when used in combination with Aprotinin.
TheophyllineThe serum concentration of Theophylline can be decreased when it is combined with Aprotinin.
TianeptineThe serum concentration of Tianeptine can be increased when it is combined with Aprotinin.
TicagrelorThe therapeutic efficacy of Ticagrelor can be decreased when used in combination with Aprotinin.
TiclopidineThe therapeutic efficacy of Ticlopidine can be decreased when used in combination with Aprotinin.
TinzaparinThe therapeutic efficacy of Tinzaparin can be decreased when used in combination with Aprotinin.
TipranavirThe serum concentration of Aprotinin can be decreased when it is combined with Tipranavir.
TirofibanThe therapeutic efficacy of Tirofiban can be decreased when used in combination with Aprotinin.
TrandolaprilAprotinin may decrease the antihypertensive activities of Trandolapril.
TreprostinilThe therapeutic efficacy of Treprostinil can be decreased when used in combination with Aprotinin.
TretinoinTretinoin may increase the thrombogenic activities of Aprotinin.
TriazolamThe serum concentration of Triazolam can be increased when it is combined with Aprotinin.
TriflusalThe therapeutic efficacy of Triflusal can be decreased when used in combination with Aprotinin.
TrimipramineThe serum concentration of Trimipramine can be increased when it is combined with Aprotinin.
UrokinaseThe therapeutic efficacy of Urokinase can be decreased when used in combination with Aprotinin.
VorapaxarThe therapeutic efficacy of Vorapaxar can be decreased when used in combination with Aprotinin.
WarfarinThe therapeutic efficacy of Warfarin can be decreased when used in combination with Aprotinin.
XimelagatranThe therapeutic efficacy of Ximelagatran can be decreased when used in combination with Aprotinin.
ZidovudineThe serum concentration of Zidovudine can be decreased when it is combined with Aprotinin.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Serine-type endopeptidase activity
Specific Function:
Has activity against the synthetic substrates Boc-Phe-Ser-Arg-Mec, Boc-Leu-Thr-Arg-Mec, Boc-Gln-Ala-Arg-Mec and Boc-Val-Pro-Arg-Mec. The single-chain form is more active than the two-chain form against all of these substrates.
Gene Name:
PRSS1
Uniprot ID:
P07477
Molecular Weight:
26557.88 Da
References
  1. Mahdy AM, Webster NR: Perioperative systemic haemostatic agents. Br J Anaesth. 2004 Dec;93(6):842-58. Epub 2004 Jul 26. [PubMed:15277296 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Serine-type endopeptidase activity
Specific Function:
Not Available
Gene Name:
CTRB1
Uniprot ID:
P17538
Molecular Weight:
27869.74 Da
References
  1. Mahdy AM, Webster NR: Perioperative systemic haemostatic agents. Br J Anaesth. 2004 Dec;93(6):842-58. Epub 2004 Jul 26. [PubMed:15277296 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Serine-type peptidase activity
Specific Function:
Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In ovulation, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin ...
Gene Name:
PLG
Uniprot ID:
P00747
Molecular Weight:
90568.415 Da
References
  1. Mahdy AM, Webster NR: Perioperative systemic haemostatic agents. Br J Anaesth. 2004 Dec;93(6):842-58. Epub 2004 Jul 26. [PubMed:15277296 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Serine-type endopeptidase activity
Specific Function:
Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin.
Gene Name:
KLK1
Uniprot ID:
P06870
Molecular Weight:
28889.425 Da
References
  1. Mahdy AM, Webster NR: Perioperative systemic haemostatic agents. Br J Anaesth. 2004 Dec;93(6):842-58. Epub 2004 Jul 26. [PubMed:15277296 ]
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Drug created on February 12, 2009 09:44 / Updated on August 17, 2016 12:24