Aceclofenac (1-30 μM; 72 hours) totally inhibits prostaglandin E2 synthesis by IL-1β or LPS-stimulated human chondrocytes and considerably lowers interleukin-6 production [1]. With an IC50 value more than 100 μM, aceclofenac suppresses COX-1; nevertheless, in whole blood testing, COX-2 activity was 50% lower at a dosage of 0.77 μM [1]. In human articular chondrocytes, aceclofenac reduces nitric oxide production and enhances the synthesis of interleukin-1 receptor antagonists [2].

Aceclofenac displays a Cmax of 4.59 μg/mL following oral treatment (rat 20 mg/kg) [3]. Because of its high plasma clearance (rat 1.10 L/h/kg) upon intravenous injection (rat 10 mg/kg), aceclofenac has a terminal elimination half-life (rat 3.24 hours) [3].

Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rats, body weight 32-340 g[3]
Doses: 10 mg/kg intravenously (iv) (iv)(iv), 20 mg/kg orally (pharmacokinetic/PK/PK analysis)
Route of Administration: oral and intravenous (iv) (iv)injection
Experimental Results:T1 /2 (3.24 hrs (hrs (hours)))), Cmax (orally 4.59 μg/mL).

Absorption, Distribution and Excretion
Aceclofenac is rapidly and completely absorbed from the gastrointestinal tract and circulates mainly as unchanged drug following oral administration. Peak plasma concentrations are reached around 1.25 to 3 hours post-ingestion, and the drug penetrates into the synovial fluid where the concentration may reach up to 60% of that in the plasma. There is no accumulation in regular dosing, with similar maximum plasma concentration (Cmax) and time to reach peak plasma concentration (Tmax) after single and multiple doses.
The main route of elimination is via the urine where the elimination accounts for 70-80% of clearance of the drug. Approximately two thirds of the administered dose is excreted via the urine, mainly as glucuronidated and hydroxylated forms of aceclofenac. About 20% of the dose is excreted into feces.
The volume of distribution is approximately 25 L.
The mean clearance rate is approximately 5 L/h.

---

Metabolism / Metabolites
4'-hydroxyaceclofenac is the main metabolite detected in plasma however other minor metabolites include diclofenac, 5-hydroxyaceclofenac, 5-hydroxydiclofenac, and 4'-hydroxydiclofenac. It is probable that the metabolism of aceclofenac is mediated by CYP2C9.
Aceclofenac has known human metabolites that include diclofenac, 5-hydroxy-aceclofenac, and 4'-hydroxy-aceclofenac.

---

Biological Half-Life
The mean plasma elimination half-life is approximately 4 hours.

Protein Binding
It is reported to be highly protein-bound (>99%).

[1]. In vitro effects of aceclofenac and its metabolites on the production by chondrocytes of inflammatory mediators. Inflamm Res. 2001 Aug;50(8):391-9.

[2]. Aceclofenac increases the synthesis of interleukin 1 receptor antagonist and decreases the production of nitric oxide in human articular chondrocytes. J Rheumatol. 2001 Dec;28(12):2692-9.

[3]. Absolute bioavailability and metabolism of aceclofenac in rats. Arch Pharm Res. 2015 Jan;38(1):68-72.

Aceclofenac is a monocarboxylic acid that is the carboxymethyl ester of diclofenac. A non-steroidal anti-inflammatory drug related to diclofenac, it is used in the management of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. It has a role as an EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor, a non-steroidal anti-inflammatory drug and a non-narcotic analgesic. It is a monocarboxylic acid, a carboxylic ester, a secondary amino compound, an amino acid and a dichlorobenzene. It is functionally related to a diclofenac.
Aceclofenac is an oral non-steroidal anti-inflammatory drug (NSAID) with marked anti-inflammatory and analgesic properties used to treat osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. It is reported to have a higher anti-inflammatory action or at least comparable effects than conventional NSAIDs in double-blind studies. Aceclofenac potently inhibits the cyclo-oxygenase enzyme (COX) that is involved in the synthesis of prostaglandins, which are inflammatory mediators that cause pain, swelling, inflammation, and fever. Aceclofenac belongs to BCS Class II as it possesses poor aqueous solubility. It displays high permeability to penetrate into synovial joints where in patients with osteoarthritis and related conditions, the loss of articular cartilage in the area causes joint pain, tenderness, stiffness, crepitus, and local inflammation. Aceclofenac is also reported to be effective in other painful conditions such as dental and gynaecological conditions. In 1991, aceclofenac was developed as an analog of a commonly prescribed NSAID, [DB00586], via chemical modification in effort to improve the gastrointestinal tolerability of the drug. It is a more commonly prescribed drug in Europe.

---

Drug Indication
Aceclofenac is indicated for the relief of pain and inflammation in osteoarthritis, rheumatoid arthritis and ankylosing spondylitis.

---

Mechanism of Action
Through COX-2 inhibition, aceclofenac downregulates the production of various inflammatory mediators including prostaglandin E2 (PGE2), IL-1β, and TNF from the arachidonic acid (AA) pathway. Inhibition of IL-6 is thought to be mediated by diclofenac converted from aceclofenac. Suppressed action of inflammatory cytokines decreases the production of reactive oxygen species. Aceclofenac is shown to decreased production of nitrous oxide in human articular chondrocytes. In addition, aceclofenac interferes with neutrophil adhesion to endothelium by decreasing the expression of L-selectin (CD62L), which is a cell adhesion molecule expressed on lymphocytes. Aceclofenac is proposed to stimulate the synthesis of glycosaminoglycan in human osteoarthritic cartilage which may be mediated through its inhibitory action on IL-1 production and activity. The chrondroprotective effects are generated by 4'-hydroxyaceclofenac which suppresses IL-1 mediated production of promatrix metalloproteinase-1 and metalloproteinase-3 and interferes with the release of proteoglycan from chrondrocytes.

---

Pharmacodynamics
Aceclofenac is a NSAID that inhibits both isoforms of COX enzyme, a key enzyme involved in the inflammatory cascade. COX-1 enzyme is a constitutive enzyme involved in prostacyclin production and protective functions of gastric mucosa whereas COX-2 is an inducible enzyme involved in the production of inflammatory mediators in response to inflammatory stimuli. Aceclofenac displays more selectivity towards COX-2 (IC50 of 0.77uM) than COX-1 (IC50 of >100uM), which promotes its gastric tolerance compared to other NSAIDs. The primary metabolite, 4'-hydroxyaceclofenac, also minimally inhibits COX-2 with IC50 value of 36uM. Although the mode of action of aceclofenac is thought to mainly arise from the inhibition of synthesis of prostaglandins (PGE2), aceclofenac also inhibits the production of inflammatory cytokines, interleukins (IL-1β, IL-6), and tumor necrosis factors (TNF). It is also reported that aceclofenac also affects the cell adhesion molecules from neutrophils. Aceclofenac also targets the synthesis of glycosaminoglycan and mediates chrondroprotective effects.

C16H13CL2NO4

354.183

353.022

89796-99-6

Aceclofenac-d4

71771

White to off-white solid powder

1.5±0.1 g/cm3

486.0±45.0 °C at 760 mmHg

149-153°C

247.8±28.7 °C

0.0±1.3 mmHg at 25°C

1.639

4.16

2

5

7

23

411

0

MNIPYSSQXLZQLJ-UHFFFAOYSA-N

InChI=1S/C16H13Cl2NO4/c17-11-5-3-6-12(18)16(11)19-13-7-2-1-4-10(13)8-15(22)23-9-14(20)21/h1-7,19H,8-9H2,(H,20,21)

2-(2-(2-((2,6-dichlorophenyl)amino)phenyl)acetoxy)acetic acid

Aceclofenac Airtal BeofenacYT-919 YT919YT 919

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 (~282.34 mM)
H2O : ~0.1 mg/mL (~0.28 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.06 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 25.0 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.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (7.06 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.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (7.06 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.

---

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