Absorption, Distribution and Excretion
Rapid oral absorption with a bioavailability greater than 60%. Peak plasma concentrations are reached 1 to 3 hours after oral administration. Primarily excreted via the kidneys as metabolites. Steady-state volume of distribution is significantly dose-dependent: 78 ml/kg for doses ≤20 μg/kg and 88 ml/kg for doses >20 μg/kg. Acenocoumarol is primarily excreted unchanged via the kidneys. In rats, 1 mg of the R- or S-enantiomer of acetononitrocoumarin was subcutaneously injected, and its bile and urinary excretion patterns were investigated. Within 24 hours, 50% was excreted bile and 20% urinarily, with no significant difference in metabolic pattern or metabolite content. Minor differences due to stereochemical variations have been noted. Metabolism/Metabolites Extensively metabolized in the liver, it is oxidized to produce two hydroxy metabolites and reduced to two alcohol metabolites via ketone reduction. Nitro reduction produces an amino metabolite, which is further converted to an Aceprometazine metabolite. These metabolites appear to be pharmacologically inactive. It is extensively metabolized in the liver, producing two hydroxyl metabolites through oxidation and two alcohol metabolites through ketone reduction. Nitro reduction produces an amino metabolite, which is further converted to an Aceprometazine metabolite. These metabolites appear to be pharmacologically inactive. Excretion route: Primarily metabolized by the kidneys. Half-life: 8 to 11 hours. Biological half-life: 8 to 11 hours. Acenocoumarol has a shorter half-life, ranging from 10 to 24 hours.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Acenocoumarol has not been approved for marketing by the U.S. Food and Drug Administration (FDA), but it is available in Canada and other countries. Because the amount of acetononitrocoumarin in breast milk is low, the amount ingested by infants is also very small. There are currently no reports of changes in coagulation parameters or adverse reactions in breastfed infants caused by acetononitrocoumarin use by breastfeeding mothers. It is generally believed that the risk to breastfed infants from acetononitrocoumarin use by breastfeeding mothers is minimal. No special precautions are required.
◉ Effects on Breastfed Infants
Nineteen infants were breastfed (the extent of feeding was not specified) while their mothers received acetononitrocoumarin anticoagulation therapy immediately after delivery. Although these infants did not receive prophylactic vitamin K treatment at birth, all infants showed normal coagulation function (as measured by thrombosis tests) after their mothers received at least 5 days of anticoagulation therapy. Seven infants were exclusively breastfed by mothers receiving long-term anticoagulation therapy (using acetocoumarin to prevent thrombosis after heart valve replacement). All mothers received therapeutic anticoagulation, with an average weekly dose of 21 mg acetocoumarin (range 12–45 mg/week). Each infant received a prophylactic dose of 1 mg vitamin K at birth, and their prothrombin time was measured after at least 7 days of breastfeeding. The prothrombin time of these infants was not significantly different from that of a control group of 42 breastfed infants whose mothers did not receive anticoagulation therapy. No cases of bleeding were reported. ◉ Effects on lactation and breast milk
As of the revision date, no relevant published information was found.

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Protein binding
98.7% bound to protein, primarily albumin.

Acenocoumarol is a hydroxycoumarin derivative of warfarin, in which the hydrogen at the 4-position of the phenyl substituent is replaced by a nitro group. It has anticoagulant activity and is an EC 1.6.5.2 [NAD(P)H dehydrogenase (quinone)] inhibitor. It is a C-nitro compound, a hydroxycoumarin, and a methyl ketone. Acenocoumarol is a coumarin derivative used as an anticoagulant. Coumarin derivatives inhibit the reduction of vitamin K by vitamin K reductase. This prevents the carboxylation of vitamin K-dependent coagulation factors II, VII, IX, and X, thereby interfering with the coagulation process. Hematocrit, hemoglobin, international normalized ratio, and liver function indicators should be monitored. Patients taking acetononitrocoumarin are prohibited from donating blood. Acenocoumarol is a 4-hydroxycoumarin derivative with anticoagulant activity. As a vitamin K antagonist, acetononitrocoumarin inhibits vitamin K epoxide reductase, thereby inhibiting the reduction of vitamin K and the availability of vitamin KH2. This prevents the γ-carboxylation of glutamate residues near the N-terminus of vitamin K-dependent clotting factors (including factors II, VII, IX, and X, as well as anticoagulants C and S). This inhibits their activity, thereby inhibiting thrombin formation. Acenocoumarol has a shorter half-life compared to other coumarin derivatives. Acenocoumarol is a coumarin derivative used as an anticoagulant. Coumarin derivatives inhibit the reduction of vitamin K by vitamin K reductase. This prevents the carboxylation of vitamin K-dependent clotting factors II, VII, XI, and X and interferes with the coagulation process. Hematocrit, hemoglobin, international normalized ratio, and liver function indicators should be monitored. Patients taking acetononitrocoumarin are prohibited from donating blood. A coumarin used as an anticoagulant. Its action and uses are similar to warfarin. (Excerpt from Martindale Pharmacopoeia, 30th edition, p. 233)
Drug Indications
For the treatment and prevention of thromboembolic diseases. More specifically, it is indicated for the prevention of thromboembolism in cerebral embolism, deep vein thrombosis, pulmonary embolism, infarction, and transient ischemic attacks. It is used to treat deep vein thrombosis and myocardial infarction.

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Mechanism of Action
Acenocoumarol inhibits vitamin K reductase, leading to the depletion of reduced vitamin K (vitamin KH2). Since vitamin K is a cofactor for the carboxylation of N-terminal glutamate residues in vitamin K-dependent clotting factors, it limits the γ-carboxylation and subsequent activation of vitamin K-dependent clotting proteins. The synthesis of vitamin K-dependent clotting factors II, VII, IX, and X, as well as anticoagulants C and S, is inhibited, resulting in decreased prothrombin levels and reduced fibrin binding of generated thrombin. This reduces the thrombogenicity of thrombi. Oral anticoagulants block the regeneration of reduced vitamin K, leading to functional vitamin K deficiency. The mechanism by which coumarin drugs inhibit reductase is not yet clear. Some reductases are less sensitive to these drugs and only function at higher concentrations of oxidized vitamin K; this characteristic may explain why adequate vitamin K administration can counteract the effects of high doses of oral anticoagulants. /Oral Anticoagulants/
4-Hydroxycoumarin derivatives and indanedione (also known as oral anticoagulants) are both vitamin K antagonists. They are used as rodenticides by inhibiting vitamin K-dependent steps in the synthesis of various blood clotting factors. Vitamin K-dependent proteins in the coagulation cascade include procoagulant factors II (prothrombin), VII (prothrombin convertase), IX (Christmas factor), and X (Stuart-Proll factor), as well as coagulation inhibitory proteins C and S. All of these proteins are synthesized in the liver. Before being released into the bloodstream, various precursor proteins undergo numerous (intracellular) post-translational modifications. Vitamin K functions as a coenzyme in one of these modifications, specifically by carboxylating 10-12 glutamate residues to γ-carboxyglutamate (Gla) at a specific site. The presence of these Gla residues is crucial for the procoagulant activity of various coagulation factors. Vitamin K hydroquinone (KH2) is the active coenzyme, which is oxidized to vitamin K 2,3-epoxide (KO), providing the energy required for the carboxylation reaction. Subsequently, this epoxide is recycled through two reduction steps catalyzed by KO reductase… KO reductase is the target of coumarin anticoagulants. Inhibition of KO reductase by coumarin anticoagulants leads to rapid depletion of KH2, effectively preventing the formation of Gla residues. This results in the accumulation of uncarboxylated coagulation factor precursors in the liver. In some cases, these precursors are further processed without carboxylation and (depending on the species) may appear in the bloodstream. At this point, the uncarboxylated protein is called a decarboxylated coagulation factor. Normal coagulation factors circulate as proenzymes, participating in the coagulation cascade only after activation through limited proteolytic degradation. Decarboxylated coagulation factors lack procoagulant activity (i.e., cannot be activated) and cannot be converted to active proenzymes by the action of vitamin K. While high levels of circulating decarboxylation clotting factors can be detected in humans receiving anticoagulation therapy, levels of these factors are negligible in rats and mice treated with warfarin. /Anticoagulant rodenticide/

C19H15NO6

353.33

353.089

152-72-7

Acenocoumarol-d5;1185071-64-0;Acenocoumarol-d4

54676537

White to off-white solid powder

1.4±0.1 g/cm3

592.7±50.0 °C at 760 mmHg

196-199ºC

312.3±30.1 °C

0.0±1.8 mmHg at 25°C

1.656

3.15

1

6

4

26

614

0

VABCILAOYCMVPS-UHFFFAOYSA-N

InChI=1S/C19H15NO6/c1-11(21)10-15(12-6-8-13(9-7-12)20(24)25)17-18(22)14-4-2-3-5-16(14)26-19(17)23/h2-9,15,22H,10H2,1H3

4-hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]chromen-2-one

SintromG-23350SinthromeAcenocoumarinNicoumalone

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)

DMSO : ~100 mg/mL (~283.02 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.08 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.08 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (5.89 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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