Flunoxaprofen: Difference between revisions

| verifiedrevid = 444540219

| drug_name = Flunoxaprofen

| routes_of_administration =

| excretion =

| ATC_prefix = M01

| ATC_suffix = AE15

| molecular_weight = 285.269783 g/mol

'''Flunoxaprofen''', also known as Priaxim, is a [[Chiral (chemistry)|chiral]] [[non-steroidal anti-inflammatory drug]]. It is closely related to [[Naproxen]], which is also an NSAID. Flunoxaprofen has been shown to significantly improve the symptoms of [[osteoarthritis]] and [[rheumatoid arthritis]]. The clinical use of flunoxaprofen has ceased due to concerns of potential [[hepatotoxicity]].

Flunoxaprofen is a derivative of [[propionic acid]]. It is a two-ring heterocyclic compound containing [[benzoxazole]].

Because flunoxaprofen has limited water-solubility, additional steps must be taken in order to prepare syrups, creams, suppositories, etc. In order to make flunoxaprofen water-soluble, yet still active and efficient, it must be mixed with [[lysine]] and then suspended in an organic solvent that is soluble in water. A salt will crystallize upon cooling. The salt must then be filtered out and dried. Pharmacological testing of this now water-soluble compound has shown that it has anti-inflammatory properties equal to flunoxaprofen by itself.<ref name=p1>"Preparation process for making water-soluble lysine salts of (+)2-(4-fluorophenyl)-alpha-methyl-5-benzoxazole acetic acid" {{US patent|5120851}}</ref>

The efficacy and safety of flunoxaprofen has been compared with those of [[Naproxen]] in [[rheumatoid arthritis]] patients to show that the two drugs have equivalent therapeutical effects. Both drugs significantly relieve spontaneous pain which occurs both during the day and at night. Both drugs also significantly relive the pain associated with active and passive motion and aid in relieving morning stiffness. The study also showed both drugs to be equally effective at improving [[grip strength]].<ref>{{cite journal |author=Fioravanti A, Giordano N, Megale F, Jovane D, Franci A, Marcolongo R |title=[Efficacy and tolerability of flunoxaprofen in the treatment of rheumatoid arthritis. A cross-over clinical study using naproxen] |language=Italian |journal=La Clinica Terapeutica |volume=131 |issue=2 |pages=83–91 |year=1989|pmid=2533024}}</ref>

Flunoxaprofen has two enantiomers. The absorption and siposition of both enantiomers were studied in 1988. No significnat differences were seen between the absorption and elimination half-lives between the two.<ref>{{cite journal |author=Palatini P, Montanari G, Perosa A, Forgione A, Pedrazzini S, Furlanut M |title=Stereospecific disposition of flunoxaprofen enantiomers in human beings |journal=International Journal of Clinical Pharmacology Research |volume=8 |issue=3 |pages=161–7 |year=1988 |pmid=3403103}}</ref> However, further studies have shown that the S-enantiomer is the active form of the drug. Flunoxaprofen is pharmacologically activated through biotransformation of the R-enantiomer to the S-enantiomer.<ref>{{cite journal |author=Pedrazzini S, De Angelis M, Muciaccia WZ, Sacchi C, Forgione A |title=Stereochemical pharmacokinetics of the 2-arylpropionic acid non-steroidal antiinflammatory drug flunoxaprofen in rats and in man |journal=Arzneimittel-Forschung |volume=38 |issue=8 |pages=1170–5 |year=1988|pmid=3196413}}</ref> This highly stereoselective chiral inversion is mediated by the FLX-S-Acyl-CoA thioester.<ref>{{cite journal |author=Grillo MP, Wait JC, Tadano Lohr M, Khera S, Benet LZ |title=Stereoselective flunoxaprofen-S-acyl-glutathione thioester formation mediated by acyl-CoA formation in rat hepatocytes |journal=Drug Metabolism and Disposition |volume=38 |issue=1 |pages=133–42 |year=2010 |pmid=19786506 |doi=10.1124/dmd.109.029371 |pmc=2802421}}</ref>

Pharmacokinetic studies have been carried out by determining the level of propranolol enantiomers in the plasma after administering the racemic drug orally.<ref>{{cite journal |author=Martin E, Quinke K, Spahn H, Mutschler E |title=(-)-(S)-flunoxaprofen and (-)-(S)-naproxen isocyanate: two new fluorescent chiral derivatizing agents for an enantiospecific determination of primary and secondary amines |journal=Chirality |volume=1 |issue=3 |pages=223–34 |year=1989 |pmid=2642051 |doi=10.1002/chir.530010308}}</ref> It has been shown that the dextrorotatory form is particularly active and has a much higher [[therapeutic index]] than some other anti-inflammatories, including [[indomethacin]] and [[diclofenac]].<ref name=p1/>

It has also been shown that flunoxaprofen inhibits [[leukotriene]] rather than [[prostaglandin]] synthesis. This is similar to [[benoxaprofen]]. Flunoxaprofen and [[benoxaprofen]] have been shown to have similar absorption characteristics. However, the distribution and elimination of flunoxaprofen has been shown to be much faster than [[benoxaprofen]].<ref>{{cite journal |author=Furlanut M, Montanari G, Perosa A, Velussi C, Forgione A, Palatini P |title=Absorption and disposition kinetics of flunoxaprofen and benoxaprofen in healthy volunteers |journal=International Journal of Clinical Pharmacology Research |volume=5 |issue=3 |pages=165–70 |year=1985 |pmid=4018949}}</ref>

A structural analog of flunoxaprofen is [[benoxaprofen]]. The two drugs are carboxylic acid analogs that form reactive acyl glucurnonides. [[Benoxaprofen]] has been shown to be involved in rare hepatotoxicity. Because of this, [[benoxaprofen]] has been removed from the market. In response to this the clinical use of flunoxaprofen has also stopped, even though studies have shown that flunoxaprofen is less toxic than [[benoxaprofen]].

The toxicity of these [[nonsteroidal antiinflammatory drugs]] may be related to the covalent modification of proteins in response to the drugs' reactive acyl glucuronides. The reactivity of the acyl glucoronides can effect the protein binding.<ref>{{cite journal |author=Dong JQ, Liu J, Smith PC |title=Role of benoxaprofen and flunoxaprofen acyl glucuronides in covalent binding to rat plasma and liver proteins in vivo |journal=Biochemical Pharmacology |volume=70 |issue=6 |pages=937–48 |year=2005 |pmid=16046212 |doi=10.1016/j.bcp.2005.05.026}}</ref>

{{NSAIDs}}

[[Category:Organofluorides]]

[[bs:Flunoksaprofen]]