Etoricoxib

Etoricoxib is a selective cyclooxygenase-2 (COX-2) inhibitor. Etoricoxib inhibits the activity of COX-2 (IC₅₀=1.1μM) and COX-1 (IC₅₀=116μM). Etoricoxib inhibits COX-2-mediated arachidonic acid conversion to reduce the synthesis of pro-inflammatory prostaglandins such as prostaglandin E2. Etoricoxib can be used for research on osteoarthritis, rheumatoid arthritis, acute gouty arthritis, ankylosing spondylitis, and chronic pain^[1-4].

In vitro, Caco-2 cells were treated with 0.2-20μg/mL Etoricoxib for 24-48 hours. Etoricoxib did not affect ACE2 mRNA and protein expression. Etoricoxib did not affect soluble and membrane-bound ACE2 activity^[5]. N13 cells were pretreated with 6-12µM Etoricoxib for 1 hour, then stimulated with 10µg/mL lipopolysaccharide for 24-48 hours, resulting in reduced COX-2 protein expression, NF-kB phosphorylation, and NO production^[6]. Mouse bone-derived cells were treated with 10-20µM etoricoxib for 7 days, resulting in inhibited alkaline phosphatase activity^[7].

In vivo, C57BL/6 mice received intraperitoneal injections of 5-20mg/kg Etoricoxib 3 times a week for 4 weeks starting from day 2 after destabilization of the medial meniscus surgery, resulting ininhibited osteophyte formation, reduced bone volume fraction and trabecular thickness, reduced subchondral bone elastic modulus, increased subchondral bone microfractures and pores, increased the empty/total osteocyte ratio. Etoricoxib did not significantly improve articular cartilage destruction or synovial inflammation^[8]. Pentylenetetrazol-induced seizure model albino mice were orally administered 6mg/kg or 10mg/kg Etoricoxib, resulting in delayed the onset of clonic seizures, shortened clonic seizure duration, enhanced diazepam protection, reduced mortality, increased free plasma diazepam levels^[9]. BALB/c mice were orally administered 10.5-21mg/kg/day Etoricoxib for 28 days. Etoricoxib (10.5mg/kg/day) caused mild centrilobular vein and sinusoid dilation and congestion, portal area enlargement, and occasional hepatocyte vacuolation. Etoricoxib (21mg/kg/day) caused hepatocyte ballooning, pyknosis, inflammatory cell infiltration, hepatocyte necrosis, and hepatic lobule structure destruction^[10].

References:

[1] Cochrane DJ, Jarvis B, Keating GM. Etoricoxib. Drugs. 2002;62(18):2637-51; discussion 2652-3.

[2] Malviya R, Sharma PK, Dubey SK. Efficiency of self-assembled etoricoxib containing polyelectrolyte complex stabilized cubic nanoparticles against human cancer cells. Precis Med Sci. 2020;9:9-22.

[3] Md S, Alhakamy NA, Alharbi WS, et al. Development and Evaluation of Repurposed Etoricoxib Loaded Nanoemulsion for Improving Anticancer Activities against Lung Cancer Cells. Int J Mol Sci. 2021;22:13284.

[4] Arunkumar P, Indulekha S, Vijayalakshmi S, et al. Poly(caprolactone) microparticles and chitosan thermogels based injectable formulation of etoricoxib for the potential treatment of osteoarthritis. Mater Sci Eng C. 2016;62:710-722.

[5] de Bruin N, Schneider A-K, Reus P, et al. Ibuprofen, Flurbiprofen, Etoricoxib or Paracetamol Do Not Influence ACE2 Expression and Activity In Vitro or in Mice and Do Not Exacerbate In-Vitro SARS-CoV-2 Infection. Int J Mol Sci. 2022;23:1049.

[6] Calvello R, Panaro MA, Carbone ML, et al. Novel selective COX-1 inhibitors suppress neuroinflammatory mediators in LPS-stimulated N13 microglial cells. Pharmacol Res. 2012;65(1):137-148.

[7] Choi JS, Kim JY, Ahn M, et al. Celecoxib is the only nonsteroidal anti-inflammatory drug to inhibit bone progression in spondyloarthritis. BMB Rep. 2025;58(3):140-145.

[8] Liu B, Jia C, Shao Y, et al. Etoricoxib decreases subchondral bone mass and attenuates biomechanical properties at the early stage of osteoarthritis in a mouse model. Biomed Pharmacother. 2020;127:110144.

[9] Jayaraman R, Manisenthil KT, Anita T, et al. Influence of etoricoxib on anticonvulsant activity of phenytoin and diazepam in experimental seizure models in mice. J Pharm Pharmacol. 2010;62(5):610-614.

[10] Jamous YF, Alghamdi BS, Jarrar Y, et al. Hepatic Effects of Etoricoxib in Mice: Integrated Histopathological and Gene Expression Analysis. Pharmaceuticals. 2026;19:414.