Enflicoxib
(Synonyms: E 6087) 目录号 : GC63804
Enflicoxib (E 6087) 是一种非甾体抗炎化合物，可选择性抑制环氧合酶 2 (COX-2)。Enflicoxib 不抑制环氧合酶-1 (COX-1)。E-6087 在动物模型中显示出抗炎、镇痛和解热活性。
Cas No.:251442-94-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Enflicoxib (E 6087) is a nonsteroidal anti-inflammatory compound that selectively inhibits cyclooxygenase-2 (COX-2). Enflicoxib does not inhibit cyclooxygenase-1 (COX-1). E-6087 shows anti-inflammatory, analgesic and antipyretic activities in animal models[1].
E-6132, one of Enflicoxib (E-6087) metabolites, also inhibits COX-2. After single oral administration of 5 mg/kg of E-6087 to rats, plasma concentrations of Enflicoxib at peak time are higher than those of E-6132, suggesting that activity is mainly due to Enflicoxib[1].Enflicoxib (E-6087) is characterized by a long elimination half-life (20-35 h), a low plasma clearance (0.10-0.22 L/h/kg) and a relatively large volume of distribution (2-6 L/kg) in rats and dogs after single oral and intravenous doses. Enflicoxib and E-6132 (a pharmacologically active metabolite) show different pharmacokinetics. The higher percentage of Enflicoxib at early times suggests that Enflicoxib is the main compound responsible for in vivo activity, although E-6132 would contribute to the activity at later times[2].
[1]. Carlos PÉrez-Maseda, et al. Determination of enantiomeric purity of a novel COX-2 anti-inflammatory drug by capillary electrophoresis using single and dual cyclodextrin systems. Electrophoresis. 2003 May;24(9):1416-21.
[2]. R F Reinoso, et al. Pharmacokinetics of E-6087, a new anti-inflammatory agent, in rats and dogs. Biopharm Drug Dispos. 2001 Sep;22(6):231-42.
| Cas No. | 251442-94-1 | SDF | Download SDF |
| 别名 | E 6087 | ||
| 分子式 | C16H12F5N3O2S | 分子量 | 405.34 |
| 溶解度 | DMSO : 100 mg/mL (246.71 mM; ultrasonic and warming and heat to 60°C) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4671 mL | 12.3353 mL | 24.6706 mL |
| 5 mM | 0.4934 mL | 2.4671 mL | 4.9341 mL |
| 10 mM | 0.2467 mL | 1.2335 mL | 2.4671 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Enflicoxib for canine osteoarthritis: A randomized, blind, multicentre, non-inferiority clinical trial compared to mavacoxib
PLoS One 2022 Sep 20;17(9):e0274800.PMID:36126039DOI:10.1371/journal.pone.0274800.
Background: This prospective, multisite, blinded, randomized, non-inferiority clinical study aimed to confirm the efficacy and safety of Enflicoxib in the treatment of pain and inflammation associated with canine osteoarthritis. A total of 180 dogs were randomized to receive Enflicoxib (n = 78), mavacoxib (n = 80) or placebo (n = 22). Dogs underwent veterinary assessments from day 0 to day 42 using a clinical sum score (CSS). Efficacy was also assessed by the owners using the Canine Brief Pain Inventory (CBPI). The primary efficacy endpoint was the overall CSS from day 0 to day 42. Results: The overall CSS expressed as area under the curve demonstrated non-inferiority of Enflicoxib compared to mavacoxib, and both showed superiority over placebo. At the end of the study, average CSS, and the percentage of CSS responders for Enflicoxib (3.64 and 74%) and mavacoxib (4.49 and 68%), was superior to placebo (7.15 and 29%). A faster onset of action was observed for Enflicoxib as superiority over placebo was evidenced from the first efficacy assessment (day 7) onwards for both parameters, whereas mavacoxib was only significantly different from day 14 onwards. According to the owner assessment, the percentage of CBPI responders was 90%, 79%, and 43% for dogs treated with Enflicoxib, mavacoxib and placebo, respectively, and superiority over placebo was demonstrated for both active treatments. In all secondary parameters, non-inferiority of Enflicoxib versus mavacoxib was confirmed. The dog's quality of life improved in all groups, but only Enflicoxib showed superiority versus placebo. When assessing severely affected dogs only, results were similar, thus confirming the efficacy of Enflicoxib in all stages of canine OA. There were no differences between groups in the frequency of adverse events, which were most frequently mild affecting the gastrointestinal tract and recovered without treatment. Conclusions: Enflicoxib is efficacious and safe for the treatment of pain and inflammation in any stage of canine osteoarthritis with a faster onset of action compared to mavacoxib.
Pharmacokinetics of Enflicoxib in dogs: Effects of prandial state and repeated administration
J Vet Pharmacol Ther 2021 Nov;44(6):888-901.PMID:34160092DOI:10.1111/jvp.12995.
The pharmacokinetics of Enflicoxib were evaluated in both a bioavailability study and a multi-dose safety study in Beagle dogs. When administered at 8 mg/kg, the oral bioavailability (F) of Enflicoxib was 44.1% in fasted dogs, but F increased to 63.4% under post prandial conditions. Enflicoxib is rapidly metabolised. After the first 48 h, the plasma levels of its pyrazol metabolite were much higher and persistent than those of the parent compound. Following intravenous administration, the total body plasma clearance of Enflicoxib was of 140 ml/h/kg and the volume of distribution based on the terminal phase was 4 L/kg. Plasma protein binding for both compounds was approximately 99%. The blood to plasma ratio for the pyrazol metabolite showed saturable kinetics with higher blood cell affinity at lower total blood concentrations which ranged from 2.49 to 0.95 for concentrations from 1 to 15 µg/ml. Enflicoxib and its pyrazol metabolite exhibited dose-proportional pharmacokinetics for single oral doses of 8-40 mg⁄kg and for multiple oral doses of 4-20 mg⁄kg. After 7 months of repeated weekly administrations, pre-dose plasma concentrations (Cmin,ss ) remained constant throughout the study, with no trend to any significant over-accumulation. The mean terminal elimination half-life (t½ ) was 20 h for Enflicoxib and 17 days for the pyrazol metabolite. The pharmacokinetic profile of Enflicoxib and its pyrazol metabolite in dogs supports the proposed dosing regimen in which doses are separated by 1 week.
Pharmacology of Enflicoxib, a new coxib drug: Efficacy and dose determination by clinical and pharmacokinetic-guided approach for the treatment of osteoarthritis in dogs based on an acute arthritis induction model
Vet Med Sci 2022 Jan;8(1):31-45.PMID:34854245DOI:10.1002/vms3.670.
Enflicoxib is a newly developed NSAID of the coxib class. The optimal therapeutic dose to be confirmed in the field studies was established using a combination of pharmacokinetic (PK) modelling and pharmacodynamic (PD) studies. First, a PK study was performed to determine the plasmatic profile of Enflicoxib and its active pyrazol metabolite in dogs. Thereafter, two studies using a urate crystal-induced acute arthritis model allowed to correlate efficacy with plasmatic concentrations. Finally, a population PK model was developed to establish the Minimum Effective Concentration (MEC) and the Maximum Tolerated Concentration (MTC). Enflicoxib plasma concentrations were highest for the first 48 h. Thereafter, pyrazol metabolite concentrations were higher and persisted up to the end of the study. No reduction on the lameness (CLS) or pain scores (PS) was observed in the first hours after Enflicoxib administration so no MEC could be established for the parent compound. Both CLS and PS were greatly reduced when the pyrazol metabolite achieved concentrations of 411 ng/ml or higher, so this concentration was established as the MEC for the pyrazol metabolite. Enflicoxib MTC was established at 6723 ng/ml whereas for the pyrazol metabolite it was 4258 ng/ml. The population PK model showed that a loading Enflicoxib dose of 8 mg/kg followed by weekly maintenance doses of 4 mg/kg would achieve stable concentrations of the pyrazol metabolite within the therapeutic window (between the MEC and the MTC), and it was considered the most adequate posology to be confirmed in the field clinical studies for the treatment of canine osteoarthritis.
Efficacy and safety of Enflicoxib for treatment of canine osteoarthritis: A 6-week randomised, controlled, blind, multicentre clinical trial
Vet Rec 2022 Sep;191(6):e949.PMID:34590318DOI:10.1002/vetr.949.
Background: Enflicoxib is a new COX-2 selective NSAID intended for the treatment of pain and inflammation associated with canine osteoarthritis. Methods: A prospective, multisite, blinded, randomised, controlled, parallel-group field study was performed to determine the efficacy and safety of Enflicoxib in canine osteoarthritis. A total of 242 dogs were randomised to receive Enflicoxib at 4 or 2 mg/kg, mavacoxib at 2 mg/kg or placebo, orally. Enflicoxib and placebo were administered once weekly from day 0 to day 35. Mavacoxib was administered on D0 and day 14. Veterinarians assessed efficacy with a numerical rating scale and owners used the Canine Brief Pain Inventory. Results: After 6 weeks, Enflicoxib at 4 mg/kg showed the highest percentage of responders as assessed by the veterinarians (68%) and the owners (84%), followed by mavacoxib (62and 83%, respectively), and Enflicoxib at 2 mg/kg (57 and 80%, respectively). All treatments reached statistical significance versus placebo, which obtained success rates of 37% and 53%, respectively. No differences in the incidence of adverse reactions were detected among the different groups. Conclusions: Enflicoxib administered weekly for 6 weeks, at 4 mg/kg PO with an initial loading dose of 8 mg/kg, is efficacious and safe for the treatment of canine osteoarthritis.
Selective inhibition of cyclooxygenase-2 by Enflicoxib, its enantiomers and its main metabolites in vitro in canine blood
J Vet Pharmacol Ther 2022 May;45(3):235-244.PMID:35038171DOI:10.1111/jvp.13042.
Enflicoxib is approved for the treatment of pain and inflammation in canine osteoarthritis. The objective of this work was to assess the mechanistic basis of Enflicoxib therapy investigating the COX inhibitory activity of Enflicoxib (racemate), its enantiomers and its main metabolites using the canine whole blood assay. The (R)-(+)-Enflicoxib enantiomer and metabolite M8 (hydroxylated pyrazoline) did not induce significant COX inhibition. Enflicoxib and its (S)-(-)-Enflicoxib enantiomer inhibited COX-1 and COX-2 with variable degree of preferential isoform inhibition, but no significant therapeutic effect is anticipated in vivo. The pyrazol metabolite showed the highest COX-2 inhibition and was the most selective (IC50 COX-1/ COX-2 ratio: 19.45). As the pyrazol metabolite shows saturable binding to red blood cells, its in vivo concentrations in plasma are lower than in whole blood. Accordingly, when applying the red blood cell partitioning, the respective IC50 and IC80 for COX-2 inhibition decreased from 2.8 µM (1129 ng/ml) and 13.4 µM (5404 ng/ml) to 0.2 µM (80.7 ng/ml) and 1.2 µM (484 ng/ml) and the selectivity ratio increased to close to 55. The corrected pyrazol metabolite IC50 and IC80 are well within the plasma levels described in treated dogs.