Identification

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Name
Aprotinin
Accession Number
DB06692
Type
Biotech
Groups
Approved, Investigational, Withdrawn
Biologic Classification
Protein Based Therapies
Other protein based therapies
Description

Aprotinin is a protein-based drug that is also known as bovine pancreatic trypsin inhibitor (BPTI). Since it demonstrates the capacity to slow fibrinolysis, it has been employed to reduce bleeding during complex surgery such as heart and liver surgery. For this use, it is typically administered by injection. The goal of using of aprotinin was subsequently to minimize end-organ damage resulting from hypotension due to blood loss in surgery and to reduce the necessity for blood transfusions during surgery. Nevertheless, the drug was formally withdrawn worldwide in May of 2008 after studies confirmed that its use enhanced the risk of complications or death. The substance is consequently made available only for very restricted research use.

Protein structure
Db06692
Protein chemical formula
C284H432N84O79S7
Protein average weight
6511.439 Da
Sequences
>Aprotinin (bovine pancreatic trypsin inhibitor)
RPDFCLEPPYTGPCKARIIRYFYNAKAGLCQTFVYGGCRAKRNNFKSAEDCMRTCGGA
Download FASTA Format
Synonyms
  • Aprotinin (bovine)
  • Aprotinin Biosynthetic
  • Aprotinin Bovine
  • Aprotinin Concentrated Solution
  • Aprotinina
  • Bovine Aprotinin
  • Bovine Pancreatic Trypsin Inhibitor
  • BPTI
  • Fibrinolysis Inhibitor
  • Trypsin Inhibitor, Pancreatic Basic
External IDs
232-994-9 / Bayer A 128 / Bayer-A-128 / Riker-52G / RP-9921
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TrasylolSolution10000 unitIntravenousNordic Group Bv1997-12-15Not applicableCanada
TrasylolSolution2000000IntravenousBayer Pharmaceuticals Corporation2007-01-092018-08-02Us
TrasylolSolution1000000IntravenousBayer Pharmaceuticals Corporation2007-01-092018-08-02Us
Trasylol Inj 10000 Kiu/mlLiquidIntravenousMiles Canada Inc. Pharmaceutical Division1981-12-311998-09-25Canada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
ArtissAprotinin (3000 kiu) + Calcium Chloride (40 mcmol) + Fibrinogen Human (125 mg) + Human Thrombin (4 unit)SolutionTopicalBaxter Laboratories2011-12-18Not applicableCanada
TisseelAprotinin (3000 kiu) + Calcium Chloride (40 mcmol) + Fibrinogen Human (125 mg) + Human Thrombin (500 unit)SolutionTopicalBaxter Laboratories2011-06-20Not applicableCanada
TisseelAprotinin (3000 kiu) + Calcium Chloride (40 mcmol) + Fibrinogen Human (125 mg) + Human Thrombin (500 unit)KitTopicalBaxter Laboratories2011-12-14Not applicableCanada
Categories
UNII
04XPW8C0FL
CAS number
9087-70-1

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.

Associated Therapies
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 serine proteases including trypsin, chymotrypsin and plasmin at a concentration of about 125,000 IU/mL, and kallikrein at 300,000 IU/mL. The inhibition of kallikrein inhibits formation of factor XIIa. This inhibits the intrinsic pathway of coagulation and fibrinolysis. Inhibition of plasmin also slows fibrinolysis.

TargetActionsOrganism
UTrypsin-1Not AvailableHumans
UChymotrypsinogen BNot AvailableHumans
UPlasminogenNot AvailableHumans
UKallikrein-1Not AvailableHumans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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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
PathwayCategory
Aprotinin Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbciximabThe therapeutic efficacy of Abciximab can be decreased when used in combination with Aprotinin.
AcebutololAprotinin may increase the bradycardic activities of Acebutolol.
AcetylcholineThe risk or severity of adverse effects can be increased when Aprotinin is combined with Acetylcholine.
AclidiniumThe therapeutic efficacy of Aclidinium can be decreased when used in combination with Aprotinin.
AgmatineThe therapeutic efficacy of Agmatine can be decreased when used in combination with Aprotinin.
Albutrepenonacog alfaAprotinin may increase the thrombogenic activities of Albutrepenonacog alfa.
AlcuroniumAprotinin may decrease the neuromuscular blocking activities of Alcuronium.
AldosteroneThe therapeutic efficacy of Aprotinin can be decreased when used in combination with Aldosterone.
Alpha-1-proteinase inhibitorAlpha-1-proteinase inhibitor may increase the thrombogenic activities of Aprotinin.
AlprenololAprotinin may increase the bradycardic activities of Alprenolol.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not 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
KEGG Drug
D02971
PubChem Substance
347910361
ChEMBL
CHEMBL1201619
Therapeutic Targets Database
DAP000185
PharmGKB
PA448472
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Aprotinin
ATC Codes
B02AB01 — Aprotinin
AHFS Codes
  • 20:28.16 — Hemostatics
FDA label
Download (108 KB)
MSDS
Download (19.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedPreventionPancreatitis1
1TerminatedTreatmentMetastatic Breast Cancer (MBC)1
2CompletedTreatmentDura Defects / Pathological Processes in the Posterior Fossa1
2CompletedTreatmentFacial Rhytidectomy (Face-lift)1
2RecruitingTreatmentBile Leak / Common Bile Duct Gall Stones / Infection NOS1
3CompletedPreventionBlood Loss,Surgical1
3CompletedTreatmentHemostasis in Participants Receiving Peripheral Vascular Expanded Polytetrafluoroethylene (ePTFE) Graft Prostheses1
3TerminatedPreventionBlood Loss,Surgical / Postoperative Hemorrhages1
3TerminatedTreatmentBlood Loss,Surgical1
3TerminatedTreatmentBlood Loss,Surgical / Postoperative Hemorrhages1
3Unknown StatusPreventionAllogeneic Blood Transfusions / Aortic Valve Replacement / Bleeding and Cardiac Surgery / Coronary Artery Bypass Graft Surgery Patients1
4CompletedTreatmentControl of Local Bleeding in Patients Undergoing Prostatectomy1
Not AvailableCompletedNot AvailableSurgery, Cardiac1
Not AvailableCompletedTreatmentAngina Pectoris / Ischaemic Heart Diseases1
Not AvailableNo Longer AvailableNot AvailablePostoperative Hemorrhages1
Not AvailableUnknown StatusNot AvailableSurgery, Cardiac1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Baxter International Inc.
  • Bayer Healthcare
Dosage forms
FormRouteStrength
SolutionTopical
KitTopical
SolutionIntravenous10000 unit
SolutionIntravenous1000000
SolutionIntravenous2000000
LiquidIntravenous
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)>100 °CNot Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
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 aga...
Gene Name
PRSS1
Uniprot ID
P07477
Uniprot Name
Trypsin-1
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
Humans
Pharmacological action
Unknown
General Function
Serine-type endopeptidase activity
Specific Function
Not Available
Gene Name
CTRB1
Uniprot ID
P17538
Uniprot Name
Chymotrypsinogen B
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
Humans
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...
Gene Name
PLG
Uniprot ID
P00747
Uniprot Name
Plasminogen
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
Humans
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
Uniprot Name
Kallikrein-1
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]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Identical protein binding
Specific Function
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name
BCHE
Uniprot ID
P06276
Uniprot Name
Cholinesterase
Molecular Weight
68417.575 Da
References
  1. Jeffrey K. Aronson (2015). Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions (16th ed.). Elsevier. [ISBN:0444537163]

Drug created on February 12, 2009 09:44 / Updated on September 17, 2019 03:54