DT-Web

DB06692 - Aprotinin


Identification
Name Aprotinin
Accession Number DB06692
Type biotech
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 The drug was temporarily withdrawn worldwide in 2007 after studies suggested that its use increased the risk of complications or death; after this was confirmed by follow-up studies, Trasylol was entirely and permanently withdrawn in May 2008, except - at least for the time being - for very restricted research use.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]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 6511.4390
Groups approved
Monoisotopic Weight 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.
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)
Protein binding Not Available
Biotransformation 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.
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of 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


Trypsin-1
Name Trypsin-1
Gene Name PRSS1
Pharmacological action unknown
Actions Not Available
References
  • Mahdy AM, Webster NR: Perioperative systemic haemostatic agents. Br J Anaesth. 2004 Dec;93(6):842-58. Epub 2004 Jul 26. - Pubmed
DTHybrid score 1.9168
Chymotrypsinogen B
Name Chymotrypsinogen B
Gene Name CTRB1
Pharmacological action unknown
Actions Not Available
References
  • Mahdy AM, Webster NR: Perioperative systemic haemostatic agents. Br J Anaesth. 2004 Dec;93(6):842-58. Epub 2004 Jul 26. - Pubmed
DTHybrid score 2.0947
Plasminogen
Name Plasminogen
Gene Name PLG
Pharmacological action unknown
Actions Not Available
References
  • Mahdy AM, Webster NR: Perioperative systemic haemostatic agents. Br J Anaesth. 2004 Dec;93(6):842-58. Epub 2004 Jul 26. - Pubmed
DTHybrid score 0.8161
Kallikrein-1
Name Kallikrein-1
Gene Name KLK1
Pharmacological action unknown
Actions Not Available
References
  • Mahdy AM, Webster NR: Perioperative systemic haemostatic agents. Br J Anaesth. 2004 Dec;93(6):842-58. Epub 2004 Jul 26. - Pubmed
DTHybrid score 0.6247

Predictions


Id Partner name Gene Name Score
791 Urokinase plasminogen activator surface receptor PLAUR 0.1841
267 Plasminogen activator inhibitor 1 SERPINE1 0.169
595 Fibrinogen alpha chain FGA 0.1553
54 Prothrombin F2 0.1044
1193 Proteinase-activated receptor 1 F2R 0.0899
2876 Membrane-bound lytic murein transglycosylase B mltB 0.0726
3133 UDP-galactopyranose mutase glf 0.0725
5099 UDP-galactopyranose mutase glf 0.0725
1074 Urokinase-type plasminogen activator PLAU 0.0723
2353 Apolipoprotein(a) LPA 0.0654
1792 Tissue-type plasminogen activator PLAT 0.062
1974 Oligopeptide transporter, kidney isoform SLC15A2 0.0573
723 Cytosolic phospholipase A2 PLA2G4A 0.05
1349 Plasminogen activator inhibitor 2 SERPINB2 0.0448
6020 Aldehyde oxidase AOX1 0.0358
3834 Nidogen-1 NID1 0.027
3011 Suppressor of tumorigenicity protein 14 ST14 0.0267
3825 Tetranectin CLEC3B 0.0245
2111 Annexin A2 ANXA2 0.0245
3826 Keratin, type II cytoskeletal 8 KRT8 0.0245
3833 Plasma serine protease inhibitor SERPINA5 0.0235
3851 Serine protease hepsin HPN 0.0215
1516 Calnexin CANX 0.0213
1244 Low-density lipoprotein receptor-related protein 2 LRP2 0.0198
3831 Low-density lipoprotein receptor-related protein 1 LRP1 0.0197
3830 Calreticulin CALR 0.0189
2324 Botulinum neurotoxin type B botB 0.017
2686 Tryptase beta-2 TPSB2 0.0162
520 UDP-N-acetylglucosamine 1-carboxyvinyltransferase murA 0.0148
2306 UDP-N-acetylglucosamine 1-carboxyvinyltransferase murA 0.0148
2367 UDP-N-acetylglucosamine 1-carboxyvinyltransferase murA 0.0148
2255 Copper amine oxidase tynA 0.0129
2914 Triosephosphate isomerase, glycosomal Not Available 0.0123
2517 Subtilisin BPN' apr 0.0103
3382 Glycolipid transfer protein GLTP 0.0099
2331 HTH-type transcriptional regulator qacR qacR 0.0076
6461 HTH-type transcriptional regulator qacR qacR 0.0076
387 Amiloride-sensitive amine oxidase [copper-containing] ABP1 0.0075
7187 Amiloride-sensitive amine oxidase [copper-containing] ABP1 0.0075
1119 Peroxiredoxin-5, mitochondrial PRDX5 0.0074
6882 Iodotyrosine dehalogenase 1 IYD 0.0071
6881 Nickel-binding periplasmic protein nikA 0.0071
6880 Alpha-amylase G-6 BH0413 0.0071
474 Acetylcholinesterase ACHE 0.0056
2889 Kallikrein-6 KLK6 0.0047
2947 Trypsin sprT 0.0047
4814 Copper transport protein ATOX1 ATOX1 0.0041
3211 3,2-trans-enoyl-CoA isomerase, mitochondrial DCI 0.0041
6264 cAMP-dependent protein kinase inhibitor alpha PKIA 0.0036
2886 Trypsin-3 PRSS3 0.0034
6263 cAMP-dependent protein kinase catalytic subunit alpha PRKACA 0.0033
2236 Casein kinase II subunit alpha CSNK2A1 0.0025
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