Absorption, Distribution and Excretion
Rapidly absorbed orally with greater than 60% bioavailability. Peak plasma levels are attained 1 to 3 hours following oral administration.
Mostly via the kidney as metabolites
The volume of distribution at steady-state appeared to be significantly dose dependent: 78 ml/kg for doses < or = 20 microg/kg and 88 ml/kg for doses > 20 microg/kg respectively
ACENOCOUMAROL IS LARGELY EXCRETED BY KIDNEYS, IN UNCHANGED FORM.
Rats received sc 1 mg doses of the R- or S-enantiomers of acenocoumarol and biliary and urinary excretion patterns were studied. In 24 hr, 50% biliary and 20% urinary excretion was observed with no gross differences in metabolic pattern or amount of metabolites. Slight differences due to stereochemistry are /noted/.

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Metabolism / Metabolites
Extensively metabolized in the liver via oxidation forming two hydroxy metabolites and keto reduction producing two alcohol metabolites. Reduction of the nitro group produces an amino metabolite which is further transformed to an acetoamido metabolite. Metabolites do not appear to be pharmacologically active.
Extensively metabolized in the liver via oxidation forming two hydroxy metabolites and keto reduction producing two alcohol metabolites. Reduction of the nitro group produces an amino metabolite which is further transformed to an acetoamido metabolite. Metabolites do not appear to be pharmacologically active.
Route of Elimination: Mostly via the kidney as metabolites
Half Life: 8 to 11 hours.

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Biological Half-Life
8 to 11 hours.
8 to 11 hours.
Acenocoumarol has a short half-life of 10 to 24 hours.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Acenocoumarol is not approved for marketing in the United States by the U.S. Food and Drug Administration, but is available in Canada and other countries. Because of the low levels of acenocoumarol in breastmilk, amounts ingested by the infant are small. No changes in coagulation measurements or adverse reactions in breastfed infants have been reported from maternal acenocoumarol use during lactation. There is a consensus that maternal acenocoumarol therapy during breastfeeding poses little risk to the breastfed infant. No special precautions are necessary.
◉ Effects in Breastfed Infants
Nineteen infants were breastfed (extent not stated) while their mothers were anticoagulated with acenocoumarol immediately postpartum. Despite not receiving prophylactic vitamin K at birth, none of the infants had abnormal blood clotting as measured by the Thrombotest after at least 5 days of maternal therapy.
Seven infants were exclusively breastfed by mothers who were receiving long-term anticoagulation with acenocoumarol for thromboprophylaxis following heart valve replacement. All women were therapeutically anticoagulated and receiving an average of 21 mg of acenocoumarol per week (range 12 to 45 mg per week). Each infant received 1 mg of vitamin K prophylactically at birth and had their prothrombin time measured after at least 7 days of breastfeeding. The prothrombin times of the infants was not different from those of a control group of 42 breastfed infants whose mothers were not anticoagulated. No instances of bleeding were reported.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
98.7% protein bound, mainly to albumin

Acenocoumarol is a hydroxycoumarin that is warfarin in which the hydrogen at position 4 of the phenyl substituent is replaced by a nitro group. It has a role as an anticoagulant and 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 carboxylation of vitamin K-dependent clotting factors, II, VII, IX and X, and interferes with coagulation. Hematocrit, hemoglobin, international normalized ratio and liver panel should be monitored. Patients on acenocoumarol are prohibited from giving blood.
Acenocoumarol is a 4-hydroxycoumarin derivative with anticoagulant activity. As a vitamin K antagonist, acenocoumarol inhibits vitamin K epoxide reductase, thereby inhibiting the reduction of vitamin K and the availability of vitamin KH2. This prevents gamma carboxylation of glutamic acid residues near the N-terminals of the vitamin K-dependent clotting factors, including factor II, VII, IX, and X and anticoagulant proteins C and S. This prevents their activity and thus thrombin formation. Compared to other coumarin derivatives, acenocoumarol has a short half-life.
Acenocoumarol is a coumarin derivative used as an anticoagulant. Coumarin derivatives inhibit the reduction of vitamin K by vitamin K reductase. This prevents carboxylation of vitamin K-dependent clotting factors, II, VII, XI and X, and interferes with coagulation. Hematocrit, hemoglobin, international normalized ratio and liver panel should be monitored. Patients on acenocoumarol are prohibited from giving blood.
A coumarin that is used as an anticoagulant. Its actions and uses are similar to those of WARFARIN. (From Martindale, The Extra Pharmacopoeia, 30th ed, p233)

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Drug Indication
For the treatment and prevention of thromboembolic diseases. More specifically, it is indicated for the prevention of cerebral embolism, deep vein thrombosis, pulmonary embolism, thromboembolism in infarction and transient ischemic attacks. It is used for the treatment of deep vein thrombosis and myocardial infarction.

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Mechanism of Action
Acenocoumarol inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent clotting factors, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited resulting in decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.
The oral anticoagulants block the regeneration of reduced vitamin K and thereby induce a state of functional vitamin K deficiency. The mechanism of the inhibition of reductase(s) by the coumarin drugs is not known. There exist reductases that are less sensitive to these drugs but that act only at relatively high concentrations of oxidized vitamin K; this property may explain the observation that administration of sufficient vitamin K can counteract even large doses of oral anticoagulants. /Oral Anticoagulants/
Both 4-hydroxycoumarin derivatives and indandiones (also known as oral anticoagulants) are antagonists of vitamin K. Their use as rodenticides is based on the inhibition of the vitamin K-dependent step in the synthesis of a number of blood coagulation factors. The vitamin K-dependent proteins ...in the coagulation cascade... are the procoagulant factors II (prothrombin), VII (proconvertin), IX (Christmas factor) and X (Stuart-Prower factor), and the coagulation-inhibiting proteins C and S. All these proteins are synthesized in the liver. Before they are released into the circulation the various precursor proteins undergo substantial (intracellular) post-translational modification. Vitamin K functions as a co-enzyme in one of these modifications, namely the carboxylation at well-defined positions of 10-12 glutamate residues into gamma-carboxyglutamate (Gla). The presence of these Gla residues is essential for the procoagulant activity of the various coagulations factors. Vitamin K hydroquinone (KH2) is the active co-enzyme, and its oxidation to vitamin K 2,3-epoxide (KO) provides the energy required for the carboxylation reaction. The epoxide is than recycled in two reduction steps mediated by the enzyme KO reductase... . The latter enzyme is the target enzyme for coumarin anticoagulants. Their blocking of the KO reductase leads to a rapid exhaustion of the supply of KH2, and thus to an effective prevention of the formation of Gla residues. This leads to an accumulation of non-carboxylated coagulation factor precursors in the liver. In some cases these precursors are processed further without being carboxylated, and (depending on the species) may appear in the circulation. At that stage the under-carboxylated proteins are designated as descarboxy coagulation factors. Normal coagulation factors circulate in the form of zymogens, which can only participate in the coagulation cascade after being activated by limited proteolytic degradation. Descarboxy coagulation factors have no procoagulant activity (i.e. they cannot be activated) and neither they can be converted into the active zymogens by vitamin K action. Whereas in anticoagulated humans high levels of circulating descarboxy coagulation factors are detectable, these levels are negligible in warfarin-treated rats and mice. /Anticoagulant rodenticides/

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

113.33

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)

配方 1 中的溶解度: ≥ 2.5 mg/mL (7.08 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (7.08 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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配方 3 中的溶解度: ≥ 2.08 mg/mL (5.89 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清的DMSO储备液加入到400 μL PEG300中，混匀；再向上述溶液中加入50 μL Tween-80，混匀；然后加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。