Disease relevance of C13001

• Aceclofenac: a reappraisal of its use in the management of pain and rheumatic disease [1].
• Long term NSAID treatment inhibits COX-2 synthesis in the knee synovial membrane of patients with osteoarthritis: differential proinflammatory cytokine profile between celecoxib and aceclofenac [2].
• Anaphylactic reaction after aceclofenac intake [3].
• Photoallergic contact dermatitis from aceclofenac [4].
• Allergic contact dermatitis due to aceclofenac [5].

High impact information on C13001

• CONCLUSIONS: Inhibition of COX isozymes by aceclofenac requires conversion into diclofenac [6].
• RESULTS: In short-term in vitro assays, neither aceclofenac nor 4'-hydroxy-aceclofenac affected COX-1 or COX-2, whereas diclofenac and 4'-hydroxy-diclofenac inhibited both isoforms [6].
• METHODS: Hepatocytes isolated from programmed liver biopsies were incubated with aceclofenac, and the metabolites formed were investigated by HPLC [7].
• RESULTS: The relative abundance of oxidized metabolites in vitro (i.e. 4'OH-aceclofenac + 4'OH-diclofenac vs. total hydroxylated metabolites; Spearman's p = 0.855), as well the hydrolysis of aceclofenac (4'OH-diclofenac vs. 4'OH-aceclofenac + 4'OH-diclofenac; p = 0.691) correlated well with in vivo data [7].
• Although the incidence of GI adverse events with aceclofenac was similar to those of comparator NSAIDs in individual clinical trials, withdrawal rates due to these events were significantly lower with aceclofenac than with ketoprofen and tenoxicam [1].

Chemical compound and disease context of C13001

• The overall response of patients' osteoarthritis to aceclofenac was found to be statistically superior to diclofenac by both physician and patient [8].
• CONCLUSIONS: Aceclofenac (100mg) and naproxen (500mg) effectively treated the pain associated with primary dysmenorrhoea, and both were more effective than placebo at easing menstrual pain assessed by various pain relief criteria [9].
• On completion of the study, patients in both aceclofenac and piroxicam-treated groups exhibited significant improvement in pain intensity and functional capacity of the affected knee, as represented by the Osteoarthritis Severity Index (OSI) (p < 0.0001 and p < 0.001 respectively) [10].
• The comparative efficacy of aceclofenac and ibuprofen in postoperative pain after third molar surgery [11].
• In addition, aceclofenac was found to be highly active against sodium urate-induced synovitis in dogs and adjuvant-induced polyarthritis in rats, both prophylactically and therapeutically [12].

Biological context of C13001

• Aceclofenac ([2-(2',6'-dichlorophenylamino)phenyl]acetoxyacetic acid) is a novel nonsteroidal antiinflammatory drug, the pharmacokinetics and drug metabolism of which show species differences [13].
• Aceclofenac had a faster and more potent effect than the other NSAID studied, mainly on the expression of cell adhesion molecules [14].
• Furthermore, all drugs tested, excepted ACLO, lowered lipid peroxidation induced by Fe2+/ascorbate system [15].
• Bioequivalence of two aceclofenac tablet formulations after a single oral dose to healthy male Korean volunteers [16].
• On the other hand, aceclofenac and diclofenac weakly inhibited purified ovine cyclooxygenases with IC50 values superior to 100 microM, whereas 4'-hydroxyaceclofenac was without effect [17].

Anatomical context of C13001

• 4'-Hydroxy aceclofenac suppresses the interleukin-1-induced production of promatrix metalloproteinases and release of sulfated-glycosaminoglycans from rabbit articular chondrocytes [18].
• Neutrophil aggregation induced with anti-CD43 Mab was also significantly inhibited by aceclofenac [14].
• In the rat, the most efficient aceclofenac-hydrolyzing activity is found in hepatic microsomes (Vmax = 2113 +/- 177 pmol/min/mg protein and KM = 191 +/- 40 microM) and cytosol (Vmax = 479 +/- 37 pmol/min/mg protein and KM = 75 +/- 22 microM) [13].
• In vitro adhesion assays were developed to examine the effects of aceclofenac on both neutrophil adhesion to tumor necrosis factor alpha stimulated human umbilical vein endothelial cells under nonstatic conditions, and homotypic neutrophil aggregation induced by anti-ICAM-3 and anti-CD18 monoclonal antibodies (Mab) [14].
• Patients taking aceclofenac had significantly fewer central nervous system related adverse events than patients treated with indomethacin (p < 0.001) [19].

Associations of C13001 with other chemical compounds

• METHODS: 310 outpatients with active AS were enrolled in a 3 month, multicenter, parallel, double blind trial and were randomly assigned to receive aceclofenac (200 mg daily) or indomethacin (100 mg daily) [19].
• We investigated the possible effects of 3 different nonsteroidal antiinflammatory drugs (NSAID; aceclofenac, piroxicam, aspirin) on IL-1Ra and NO production in human articular chondrocytes [20].
• The activity and tolerability of aceclofenac, a new arylacetic anti-inflammatory drug, was assessed in the treatment of post-episiotomal pain in a controlled double-blind study with paracetamol [21].
• The second was the spectrofluorimetric method in which samples of etodolac in ethanol showed native fluorescence at a lambda = 345 nm when excitation was at 235 nm and samples of aceclofenac in the phosphate buffer pH 8 showed native fluorescence at lambda = 355 nm when excitation was at 250 nm [22].
• RESULTS: 4'-Hydroxy aceclofenac, a major metabolite of aceclofenac, down-regulated both basal and IL-1beta-induced production of proMMP-1 and proMMP-3 at a concentration sufficient to suppress PGE2 production without modulating proMMP-2 or TIMP-1, whereas aceclofenac itself had no marked effect on the production of proMMPs [23].

Gene context of C13001

• In long-term in vitro assays, aceclofenac and 4'-hydroxy-aceclofenac suppressed both COX isoforms [6].
• Aceclofenac increases the synthesis of interleukin 1 receptor antagonist and decreases the production of nitric oxide in human articular chondrocytes [20].
• In the whole blood test, aceclofenac and 4'-hydroxyaceclofenac weakly inhibited COX-1 with IC50 values superior to 100 microM, but decreased by 50% COX-2 activity at the concentration of 0.77 and 36 microM, respectively [17].
• Aceclofenac induced a dramatic decrease of L-selectin expression, whereas a moderate and slight decrement of CD43 and ICAM-3 expression was also observed [14].
• OBJECTIVE: To perform a modelled economic analysis of the efficacy and tolerability of aceclofenac in comparison with those of other nonsteroidal antiinflammatory drugs (NSAIDs) used in the treatment of common arthritic disorders including osteoarthritis, rheumatoid arthritis and ankylosing spondylitis [24].

Analytical, diagnostic and therapeutic context of C13001

• Aceclofenac is well tolerated, with encouraging reports of improved general and GI tolerability relative to other NSAIDs from a meta-analysis of double-blind trials and from large nonblind studies [1].
• After oral administration to human volunteers (100 mg, single dose), aceclofenac reached a Cmax value of 7.6 +/- 1.3 micrograms/ml and a tmax of 2.6 +/- 1 [25].
• 8. The same metabolites as those detected in cell culture or microsome incubations were found in 12-hr urine after an oral administration of 100 mg aceclofenac to human volunteers [25].
• Plasma concentrations of aceclofenac were monitored by high-performance liquid chromatography over a period of 24 hours after the administration [16].
• To evaluate and compare the pharmacokinetics of acelofenac-loaded soft capsules with the conventional aceclofenac tablets (Dae-Woong Pharm. Co. Ltd., Airtal) in human subjects; 14 normal healthy male volunteers (age 20-25 years old) were divided into two groups and a randomized 2 x 2 cross-over study was performed [26].

References