Flufenamic acid is a highly polymorphic drug molecule with multiple structurally characterized polymorphic modifications.[4] It has a unique chemical structure and stands out among fenamates.[5] Nowadays, eight polymorphic forms are known that are determined by different conformers,[6][7] which makes flufenamic acid unique among other low-molecular medicinal compounds.[8][9] A fundamental feature of the structure of flufenamic acid, which has generated significant interest in the design and development of drugs,[10] is the presence of a trifluoromethyl group. Compounds with fluorine-containing substituents are known to have promising chemical and biological properties,[11][12] since such groups often improve the pharmacokinetics and bioavailability of drugs.[13] Studies have shown the promise of repositioning flufenamic acid and the use of drugs based on it in the treatment of Bartter syndrome.
Until recently, FFA was actively used in medical practice as an analgesic with anti-inflammatory and antipyretic effects.[14] FFA has been proven effective in treating rheumatoid arthritis, osteoarthritis and other inflammation-related diseases.[15] However, despite this, the use of FFA in the United States and other countries[16] is limited since the compound causes frequent side effects. The rate of gastrointestinal side effects can be as high as 60%,[17] manifested as at least one of the following: dyspepsia, nausea, abdominal pain and discomfort, constipation, diarrhoea, flatulence, indigestion, epigastric distress, stomatitits and anorexia.[17] Besides gastrointestinal side effects, the drug can cause headache, dizziness and peripheral oedema.[17]
It is not widely used in humans as it has a high rate (30–60%) of gastrointestinal side effects.[18] It is generally not available in the US.[2] It is available in some Asian and European countries as ageneric drug.[19]
^ab"Mefenamic Acid".LiverTox Database. U.S. National Institutes of Health (NIH). June 23, 2015.PMID31643176. Archived fromthe original on August 31, 2015. RetrievedJuly 3, 2015.(fenamates generally not available in the United States, such as tolfenamic acid and flufenamic acid)
^Serezhkin VN, Savchenkov AV (June 3, 2015). "Application of the Method of Molecular Voronoi–Dirichlet Polyhedra for Analysis of Noncovalent Interactions in Crystal Structures of Flufenamic Acid—The Current Record-Holder of the Number of Structurally Studied Polymorphs".Crystal Growth & Design.15 (6):2878–2882.Bibcode:2015CrGrD..15.2878S.doi:10.1021/acs.cgd.5b00326.ISSN1528-7483.S2CID100245760.
^Pippione AC, Carnovale IM, Bonanni D, Sini M, Goyal P, Marini E, et al. (April 2018). "Potent and selective aldo-keto reductase 1C3 (AKR1C3) inhibitors based on the benzoisoxazole moiety: application of a bioisosteric scaffold hopping approach to flufenamic acid".European Journal of Medicinal Chemistry.150:930–945.doi:10.1016/j.ejmech.2018.03.040.hdl:10454/16082.PMID29602039.S2CID4690397.
^Altomonte S, Zanda M (November 2012). "Synthetic chemistry and biological activity of pentafluorosulphanyl (SF5) organic molecules".Journal of Fluorine Chemistry.143:57–93.doi:10.1016/j.jfluchem.2012.06.030.hdl:2164/2557.
^Nechipadappu SK, Tekuri V, Trivedi DR (May 2017). "Pharmaceutical Co-Crystal of Flufenamic Acid: Synthesis and Characterization of Two Novel Drug-Drug Co-Crystal".Journal of Pharmaceutical Sciences.106 (5):1384–1390.Bibcode:2017JPhmS.106.1384N.doi:10.1016/j.xphs.2017.01.033.PMID28185907.
^Maestrelli F, Rossi P, Paoli P, De Luca E, Mura P (February 2020). "The role of solid state properties on the dissolution performance of flufenamic acid".Journal of Pharmaceutical and Biomedical Analysis.180 113058.doi:10.1016/j.jpba.2019.113058.PMID31881398.S2CID209499101.
