Absorption, Distribution and Excretion
100% (Intravenous Injection)
After a single intravenous injection of radiolabeled aprotinin, approximately 25-40% of the radioactive material is excreted in the urine within 48 hours. After a 30-minute infusion of 1 million KIU, approximately 2% is excreted unchanged. After a 30-minute infusion of 2 million KIU, the amount of unchanged aprotinin excreted in the urine is approximately 9% of the total dose.
After intravenous injection, aprotinin rapidly distributes throughout the extracellular space, leading to a rapid decrease in plasma aprotinin concentration.
After a single intravenous injection of radiolabeled aprotinin, approximately 25-40% of the radioactive material is excreted in the urine within 48 hours. After a 30-minute infusion of 1 million KIU, approximately 2% is excreted unchanged. After a larger dose of 2 million KIU infusion over 30 minutes, the amount of unchanged aprotinin excreted in the urine is approximately 9% of the total dose. Animal studies have shown that aprotinins primarily accumulate in the kidneys. After glomerular filtration, aprotinins are actively reabsorbed by the proximal tubules and stored in phagolysosomes. Currently, there are no studies on the distribution of aprotinins in breast milk. For more complete data on the absorption, distribution, and excretion of aprotinins (9 in total), please visit the HSDB record page. Metabolites/Metabolites: Aprotinins are primarily degraded slowly by lysosomal enzymes. Renal physiological processing of aprotinins is similar to that of other small proteins, such as insulin. Biological Half-Life: After the distribution phase, the plasma half-life of aprotinins is approximately 150 minutes. At a later time point (i.e., more than 5 hours after administration), there is a terminal elimination phase with a half-life of approximately 10 hours. After this distribution phase, a plasma half-life of approximately 150 minutes is observed. At a later time point (i.e., more than 5 hours after administration), there is a terminal elimination phase with a half-life of approximately 10 hours.

[1]. Reversible inhibition of trypsin activity with soybean flour in hide bating process for leather quality improvement. Industrial Crops and Products, Volume 161, March 2021, 113222.

Aprotinin is a protein drug, also known as bovine trypsin inhibitor (BPTI). Due to its ability to slow fibrinolysis, it was once used to reduce bleeding during complex surgeries, such as heart and liver surgeries. Aprotinin is typically administered by injection. The initial purpose of using aprotinin was to minimize end-organ damage caused by hypotension due to blood loss during surgery and to reduce the need for transfusions during surgery. However, after studies demonstrated that its use increased the risk of complications or death, the drug was officially withdrawn from the market globally in May 2008. Therefore, this substance is currently only used for very limited research purposes. Aprotinin is a single-chain polypeptide isolated from bovine lungs with antifibrinolytic and anti-inflammatory activities. As a broad-spectrum serine protease inhibitor, bovine aprotinin competitively and reversibly inhibits the activity of various esterases and proteases, including trypsin, chymotrypsin, kallikrein, plasminogen activator, tissue plasminogen activator, and tissue and leukocyte proteases, thereby attenuating the systemic inflammatory response (SIR), fibrinolysis, and thrombin generation. This drug also inhibits the release of pro-inflammatory cytokines and maintains glycoprotein homeostasis. Drug Indications For prophylactic use to reduce perioperative blood loss and transfusion requirements in patients undergoing cardiopulmonary bypass surgery, particularly those at high risk of bleeding and transfusion. FDA Label Mechanism of Action Aprotinin inhibits serine proteases (including trypsin, chymotrypsin, and plasmin) at a concentration of approximately 125,000 IU/mL and kallikrein at a concentration of 300,000 IU/mL. Inhibition of kallikrein inhibits factor XIIa production, thereby inhibiting endogenous pathways of coagulation and fibrinolysis. Inhibition of plasmin also slows fibrinolysis. Aprotinin is a broad-spectrum protease inhibitor that modulates the systemic inflammatory response (SIR) associated with cardiopulmonary bypass (CPB). SIR leads to the mutual activation of hemostasis, fibrinolysis, and cellular and humoral inflammatory systems. Aprotinin attenuates inflammatory responses, fibrinolysis, and thrombin generation by inhibiting various mediators, such as kallikrein and plasminogen activator. Aprotinin inhibits the release of pro-inflammatory cytokines and maintains glycoprotein homeostasis. In platelets, aprotinin reduces the loss of glycoproteins (e.g., GpIb, GpIIb/IIIa); in granulocytes, it inhibits the expression of pro-inflammatory adhesion glycoproteins (e.g., CD11b). The use of aprotinin in cardiopulmonary bypass reduces inflammatory responses, thereby reducing the need for allogeneic transfusions, bleeding volume, and the number of re-exploration of the mediastinum due to bleeding. Aprotinin is thought to improve hemostasis during and after cardiopulmonary bypass by protecting platelet membrane receptors that maintain platelet adhesion and aggregation. Furthermore, aprotinin also inhibits fibrinolysis by inhibiting plasminogen activator and plasma and tissue kallikrein. Because of its action on kallikrein, aprotinin can also inhibit the activation of the intrinsic coagulation system (i.e., the contact phase of coagulation), which both initiates the coagulation process and promotes fibrinolysis. The relative contribution of these effects of aprotinin to its therapeutic efficacy remains to be further elucidated. For more complete data on the mechanisms of action of aprotinins (a total of 6), please visit the HSDB record page.

6510.051

9035-81-8

169492845

White to off-white solid powder

>100 °C

-25.4

93

97

111

454

16700

57

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ZPNFWUPYTFPOJU-ZRPLRCOFSA-N

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(3R)-4-[[(2S)-1-[[(1R,2aR,4R,5aR,8aR,11aR,13R,14aR,16S,17aR,19S,20aS,25S,26aS,29aS,31S,32aS,34S,35aS,37R,38aS,41aS,42R,44aS,45R,47aR,48S,50aS,51R,53aS,54R,56aR,57S,59aR,60S,62aS,63S,66S,69S,72S,75S,78S,81S,84S,87S,90S,93R)-29a,62a,69,84-tetrakis(4-aminobutyl)-35a,75,78-tris(2-amino-2-oxoethyl)-14a-(3-amino-3-oxopropyl)-8a,41a,72-tribenzyl-50a-[(2S)-butan-2-yl]-53a-[(2R)-butan-2-yl]-47a,48,56a,81,90-pentakis(3-carbamimidamidopropyl)-31,60-bis(2-carboxyethyl)-42-[[2-[[2-[[(1R)-1-carboxyethyl]amino]-2-oxoethyl]amino]-2-oxoethyl]carbamoyl]-57-(carboxymethyl)-11a,45-bis[(1R)-1-hydroxyethyl]-13-[(1S)-1-hydroxyethyl]-66-(hydroxymethyl)-2a,16,38a,44a-tetrakis[(4-hydroxyphenyl)methyl]-26a,32a,59a,63,87-pentamethyl-20a,34-bis(2-methylpropyl)-51-(2-methylsulfanylethyl)-1a,3,4a,7a,9,10a,12,13a,15,16a,18,19a,22a,24,25a,28a,30,31a,33,34a,36,37a,40a,43a,44,46a,47,49a,50,52a,53,55a,56,58a,59,61a,62,64a,65,68,71,74,77,80,83,86,89,92,95,98-pentacontaoxo-5a-propan-2-yl-39,40,66a,67a,70a,71a-hexathia-a,2,3a,6a,8,9a,11,12a,14,15a,17,18a,21a,23,24a,27a,29,30a,32,33a,35,36a,39a,42a,43,45a,46,48a,49,51a,52,54a,55,57a,58,60a,61,63a,64,67,70,73,76,79,82,85,88,91,94,97-pentacontazahexacyclo[91.71.4.454,117.04,8.019,23.025,29]doheptacontahectan-37-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-[[(2S)-1-[(2S)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]-4-oxobutanoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O: 100 mg/mL

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)