上市后研究表明，依托度酸的环氧合酶抑制作用对 COX-2 有一定的选择性，就像塞来昔布和其他“COX-2 抑制剂”一样。与罗非考昔相比，依托度酸和塞来昔布都被归类为对 COX-2 具有“优先选择性”，并且可以完全抑制 COX-1。在肝癌细胞中，依托度酸的 r 对映体（对 COX 无活性）可抑制 β-连环蛋白的表达。

在机械性异常性疼痛小鼠模型中，依托度酸通过不依赖于 COX 的途径减轻紫杉醇诱导的周围神经病变。依托度酸和其他非甾体抗炎药以剂量依赖性方式抑制佐剂关节炎大鼠的爪肿胀并引起胃粘膜损伤。在这些非甾体抗炎药中，依托度酸在关节炎大鼠中显示出最高的 UD(50) 值和安全指数。依托度酸还显示出最高的 UD(50) 值和安全指数，除非通过乙酸诱导的正常大鼠扭体来评估其效果。依托度酸剂量依赖性地抑制胃癌的发展，在 30 mg/kg/天的剂量下没有检测到癌症。依托度酸不影响炎症细胞浸润或氧化性 DNA 损伤的程度，但它显着抑制粘膜细胞增殖，并以剂量依赖性方式抑制幽门螺杆菌 (Hp) 感染的蒙古沙鼠 (MG) 胃中肠化生的发展。依托度酸减轻CCI大鼠热诱发的痛觉过敏，CCI侧TRAP阳性多核破骨细胞数量的增加被消除，但不抑制骨矿物质含量（BMC）和骨矿物质密度（BMD）的降低。 ）在 CCI 端。

Absorption, Distribution and Excretion
Based on mass balance studies, the systemic bioavailability of etodolac from either the tablet or capsule formulation is at least 80%.
It is not known whether etodolac is excreted in human milk; however, based on its physical-chemical properties, excretion into breast milk is expected. Etodolac is extensively metabolized in the liver. The hydroxylated-etodolac metabolites undergo further glucuronidation followed by renal excretion and partial elimination in the feces (16% of dose). Approximately 1% of a etodolac dose is excreted unchanged in the urine with 72% of the dose excreted into urine as parent drug plus metabolite.
390 mL/kg
Oral cl=49.1 mL/h/kg [Normal healthy adults]
Oral cl=49.4 mL/h/kg [Healthy males (18-65 years)]
Oral cl=35.7 mL/h/kg [Healthy females (27-65 years)]
Oral cl=45.7 mL/h/kg [Eldery (>65 years)]
Oral cl=58.3 mL/h/kg [Renal impairement (46-73 years)]
Oral cl=42.0 mL/h/kg [Hepatic impairement (34-60 years)]

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Metabolism / Metabolites
Etodolac is extensively metabolized in the liver. Renal elimination of etodolac and its metabolites is the primary route of excretion (72%). Metabolites found in urine (with percents of the administered dose) are: unchanged etodolac (1%), etodolac glucuronide (13%), hydroxylated metabolites (6-, 7-, and 8-OH; 5%), hydroxylated metabolite glucuronides (20%), and unidentified metabolites (33%). Fecal excretion accounts for 16% of its elimination.
Etodolac has known human metabolites that include (2S,3S,4S,5R)-6-[2-(1,8-Diethyl-4,9-dihydro-3H-pyrano[3,4-b]indol-1-yl)acetyl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid.

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Biological Half-Life
Terminal t_1/2, 7.3 ± 4.0 hours. Distribution t_1/2, 0.71 ± 0.50 hours

Hepatotoxicity
Prospective studies show that 1% to 2% of patients taking etodolac experience at least transient serum aminotransferase elevations. These may resolve even with drug continuation. Marked aminotransferase elevations (>3 fold elevated) occur in
Likelihood score: C (probable rare cause clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because no information is available on the use of etodolac during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
> 99% bound, primarily to albumin

[1]. Biochemical and pharmacological profile of a tetrasubstituted furanone as a highly selective COX-2 inhibitor. Br J Pharmacol. 1997 May;121(1):105-17.

[2]. Etodolac, a cyclooxygenase-2 inhibitor, attenuates paclitaxel-induced peripheral neuropathy in a mouse model of mechanical allodynia. J Pharmacol Exp Ther. 2012 Jul;342(1):53-60.

[3]. Preventive effects of etodolac, a selective cyclooxygenase-2 inhibitor, on cancer development in extensive metaplastic gastritis, a Helicobacter pylori-negative precancerous lesion. Int J Cancer. 2010 Mar 15;126(6):146.

[4]. Administration of the selective cyclooxygenase (COX)-2 inhibitor etodolac prolongs cardiac allograft survival in a mouse model. Mol Med Report. 2010 Sep-Oct;3(5):771-4.

Etodolac can cause developmental toxicity and female reproductive toxicity according to state or federal government labeling requirements.
Etodolac is a monocarboxylic acid that is acetic acid in which one of the methyl hydrogens is substituted by a 1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl moiety. A preferential inhibitor of cyclo-oxygenase 2 and non-steroidal anti-inflammatory, it is used for the treatment of rheumatoid arthritis and osteoarthritis, and for the alleviation of postoperative pain. Administered as the racemate, only the (S)-enantiomer is active. It has a role as a non-steroidal anti-inflammatory drug, a cyclooxygenase 2 inhibitor, a non-narcotic analgesic and an antipyretic. It is a monocarboxylic acid and an organic heterotricyclic compound.
Etodolac is a non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic and antipyretic properties. Its therapeutic effects are due to its ability to inhibit prostaglandin synthesis. It is indicated for relief of signs and symptoms of rheumatoid arthritis and osteoarthritis.
Etodolac is a Nonsteroidal Anti-inflammatory Drug. The mechanism of action of etodolac is as a Cyclooxygenase Inhibitor.
Etodolac is a nonsteroidal antiinflammatory drug (NSAID) that is available by prescription only and is used long term for therapy of chronic arthritis and short term for acute pain. Etodolac has been linked to rare instances of clinically apparent drug induced liver disease.
Etodolac is a pyranocarboxylic acid and non-steroidal anti-inflammatory drug (NSAID) with antipyretic and analgesic activities. Etodolac inhibits the activity of cyclooxygenase I and II, thereby preventing the formation of prostaglandin which is involved in the induction of pain, fever, and inflammation. It also inhibits platelet aggregation by blocking platelet cyclooxygenase and the subsequent formation of thromboxane A2.
A non-steroidal anti-inflammatory agent and cyclooxygenase-2 (COX-2) inhibitor with potent analgesic and anti-arthritic properties. It has been shown to be effective in the treatment of OSTEOARTHRITIS; RHEUMATOID ARTHRITIS; ANKYLOSING SPONDYLITIS; and in the alleviation of postoperative pain (PAIN, POSTOPERATIVE).

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Drug Indication
For acute and long-term management of signs and symptoms of osteoarthritis and rheumatoid arthritis, as well as for the management of pain.
FDA Label

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Mechanism of Action
Similar to other NSAIDs, the anti-inflammatory effects of etodolac result from inhibition of the enzyme cycooxygenase (COX). This decreases the synthesis of peripheral prostaglandins involved in mediating inflammation. Etodolac binds to the upper portion of the COX enzyme active site and prevents its substrate, arachidonic acid, from entering the active site. Etodolac was previously thought to be a non-selective COX inhibitor, but it is now known to be 5 – 50 times more selective for COX-2 than COX-1. Antipyresis may occur by central action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat loss.

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Pharmacodynamics
Etodolac is an anti-inflammatory agent with analgesic and antipyretic properties. It is used to treat osteoarthritis, rheumatoid arthritis and control acute pain. The therapeutic effects of etodolac are achieved via inhibition of the synthesis of prostaglandins involved in fever, pain, swelling and inflammation. Etodolac is administered as a racemate. As with other NSAIDs, the S-form has been shown to be active while the R-form is inactive. Both enantiomers are stable and there is no evidence of R- to S- conversion _in vivo_.

C17H21NO3

287.35

287.152

41340-25-4

(rac)-Etodolac-d3;1276197-46-6

3308

White to off-white solid powder

1.2±0.1 g/cm3

507.9±45.0 °C at 760 mmHg

145-1480C

261.0±28.7 °C

0.0±1.4 mmHg at 25°C

1.597

3.59

62.32

2

3

4

21

400

0

NNYBQONXHNTVIJ-UHFFFAOYSA-N

InChI=1S/C17H21NO3/c1-3-11-6-5-7-12-13-8-9-21-17(4-2,10-14(19)20)16(13)18-15(11)12/h5-7,18H,3-4,8-10H2,1-2H3,(H,19,20)

(RS)-2-(1,8-Diethyl-4,9-dihydro-3H-pyrano[3,4-b]indol-1-yl)acetic 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)

配方 1 中的溶解度: ≥ 2.5 mg/mL (8.70 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 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；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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配方 2 中的溶解度: ≥ 2.5 mg/mL (8.70 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 3 中的溶解度: ≥ 2.5 mg/mL (8.70 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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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。