{{Short description|Chemical compound}} {{for|the use of trifluridine as an anti-cancer drug|Trifluridine/tipiracil}} {{redirect|Fluridine|the aquatic herbicide|fluridone}} {{redirect|F3T|the film tour|Outside (company)}} {{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 470614687 | IUPAC_name = 1-[4-Hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(trifluoromethyl)-(1''H'',3''H'')-pyrimidine-2,4-dione | image = Trifluridine structure.svg | image_class = skin-invert-image | width = 150 <!--Clinical data--> | tradename = Viroptic; Lonsurf (+tipiracil) | Drugs.com = {{drugs.com|monograph|trifluridine}} | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_US = C | pregnancy_category = | licence_EU = yes | legal_CA = Rx-only | legal_UK = <!-- GSL / P / POM / CD --> | legal_US = Rx-only | routes_of_administration = Eye drops; tablets (+tipiracil) <!--Pharmacokinetic data--> | bioavailability = Negligible (eye drops);<br />≥57% (oral) | protein_bound = >96% | metabolism = Thymidine phosphorylase | elimination_half-life = 12 minutes (eye drops);<br />1.4–2.1 hrs (combination with tipiracil) | excretion = Mostly via urine <!--Identifiers--> | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 70-00-8 | ATC_prefix = S01 | ATC_suffix = AD02 | ATC_supplemental = {{ATC|L01|BC59}}
| PubChem = 6256 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00432 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 6020 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = RMW9V5RW38 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00391 | ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI = 75179 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 1129 | synonyms = α,α,α-trifluorothymidine; 5-trifluromethyl-2′-deoxyuridine; FTD5-trifluoro-2′-deoxythymidine; TFT; CF<sub>3</sub>dUrd; FTD; F<sub>3</sub>TDR; F<sub>3</sub>Thd <!--Chemical data--> | C=10 | H=11 | F=3 | N=2 | O=5 | smiles = FC(F)(F)C=1C(=O)NC(=O)N(C=1)[C@@H]2O[C@@H]([C@@H](O)C2)CO | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C10H11F3N2O5/c11-10(12,13)4-2-15(9(19)14-8(4)18)7-1-5(17)6(3-16)20-7/h2,5-7,16-17H,1,3H2,(H,14,18,19)/t5-,6+,7+/m0/s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = VSQQQLOSPVPRAZ-RRKCRQDMSA-N }} '''Trifluridine''' (also called '''trifluorothymidine'''; abbreviation '''TFT''' or '''FTD'''<ref>{{cite journal | vauthors = Patel AK, Abhyankar R, Brais LK, Duh MS, Barghout VE, Huynh L, Yenikomshian MA, Ng K, Fuchs CS | display-authors = 6 | title = Trifluridine/Tipiracil and Regorafenib in Patients with Metastatic Colorectal Cancer: A Retrospective Study at a Tertiary Oncology Center | journal = The Oncologist | volume = 26 | issue = 12 | pages = e2161–e2169 | date = December 2021 | pmid = 34406678 | pmc = 8649060 | doi = 10.1002/onco.13942 | doi-access = free | author-link8 = Kimmie Ng }}</ref>) is an anti-herpesvirus antiviral drug, used primarily as prescription eyedrops. It was sold under the trade name '''Viroptic''' by Glaxo Wellcome, now merged into GlaxoSmithKline. The brand is now wholly owned by King Pharmaceuticals.
Trifluridine was approved for medical use in 1980.<ref>{{cite book| vauthors = Kimberlin DW | chapter = Antiviral Agents | veditors = Long SS, Pickering LK, Prober CG |title=Principles and Practice of Pediatric Infectious Disease|date=2012|publisher=Elsevier Health Sciences|isbn=978-1-4377-2702-9|page=1502| chapter-url = https://books.google.com/books?id=nQ7-o8JAH7kC&pg=PA1502|language=en}}</ref> It is also a component of the anti-cancer drug trifluridine/tipiracil, which is taken by mouth.
==Medical uses== Trifluridine eye drops are used for the treatment of keratitis and keratoconjunctivitis caused by the herpes simplex virus types 1 and 2, as well as for prevention and treatment of vaccinia virus infections of the eye.<ref name="Drugs.com" />
A Cochrane Systematic Review showed that trifluridine and aciclovir were a more effective treatment than idoxuridine or vidarabine,<ref name=Wilhelmus2015>{{cite journal | vauthors = Wilhelmus KR | title = Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis | journal = The Cochrane Database of Systematic Reviews | volume = 1 | article-number = CD002898 | date = January 2015 | issue = 1 | pmid = 25879115 | pmc = 4443501 | doi = 10.1002/14651858.CD002898.pub5 }}</ref> significantly increasing the relative number of successfully healed eyes in one to two weeks.<ref name=Wilhelmus2015></ref>
==Adverse effects== Common side effects of trifluridine eye drops include transient burning, stinging, local irritation, and edema of the eyelids.<ref name="Drugs.com" />
Adverse effects of the anti-cancer formulation have only been evaluated for the combination trifluridine/tipiracil, not for the individual components.{{cn|date=November 2022}}
== Interactions ==
Only ''in vitro'' interaction studies are available. In these, trifluridine used the concentrative nucleoside transporter 1 (CNT1) and equilibrative nucleoside transporters 1 (ENT1) and 2 (ENT2). Drugs that interact with these transporters could influence blood plasma concentrations of trifluridine. Being a thymidine phosphorylase inhibitor, trifluridine could also interact with substrates of this enzyme such as zidovudine.<ref name="AC">{{cite book|title=Austria-Codex | veditors = Haberfeld H |publisher=Österreichischer Apothekerverlag|location=Vienna|year=2015|language=German}}</ref>
For the eye drops, trifluridine absorption is negligible,<ref name="Drugs.com">{{cite web | work = Drugs.com | url = https://www.drugs.com/monograph/trifluridine.html | title = Trifluridine }}</ref> rendering interactions basically irrelevant.
==Pharmacology== {{for|the anti-cancer mechanism|Trifluridine/tipiracil#Mechanism of action}}
===Mechanism of action (eye drops)=== It is a nucleoside analogue, a modified form of deoxyuridine, similar enough to be incorporated into viral DNA replication, but the –CF<sub>3</sub> group added to the uracil component blocks base pairing, thus interfering with viral DNA replication.{{cn|date=November 2022}}
===Pharmacokinetics (eye drops)=== Trifluridine passes the cornea and is found in the aqueous humour. Systemic absorption is negligible.<ref name="Drugs.com" />
===Pharmacokinetics (oral)=== thumb|5-Trifluoromethyl-2,4(1''H'',3''H'')-pyrimidinedione (FTY), the main metabolite Pharmacokinetic data of oral trifluridine have only been evaluated in combination with tipiracil, which significantly affects biotransformation of the former. At least 57% of trifluridine are absorbed from the gut, and highest blood plasma concentrations are reached after two hours in cancer patients. The substance has no tendency to accumulate in the body. Plasma protein binding is over 96%. Trifluridine is metabolised by the enzyme thymidine phosphorylase to 5-trifluoromethyl-2,4(1''H'',3''H'')-pyrimidinedione (FTY), and also by glucuronidation. Elimination half-life is 1.4 hours on the first day and increases to 2.1 hours on the twelfth day. It is mainly excreted via the kidneys.<ref name="AC" />
Tipiracil causes C<sub>max</sub> (highest blood plasma concentrations) of trifluridine to increase 22-fold, and its area under the curve 37-fold, by inhibiting thymidine phosphorylase.<ref name="AC" />
==Chemistry== The substance is a white crystalline powder. It is freely soluble in methanol and acetone; soluble in water, ethanol, 0.01 M hydrochloric acid, and 0.01 M sodium hydroxide; sparingly soluble in isopropyl alcohol and acetonitrile; slightly soluble in diethyl ether; and very slightly soluble in isopropyl ether.<ref>{{cite web | work = Drugs.com | url = https://www.drugs.com/pro/lonsurf.html | title = Lonsurf Prescribing Information }} </ref>
== References == {{reflist}}
== External links == {{refbegin}} * {{cite journal | vauthors = Costin D, Dogaru M, Popa AS, Cijevschi I | title = [Trifluridine therapy in herpetic in keratitis] | language = ro | journal = Revista Medico-Chirurgicala a Societatii de Medici Si Naturalisti Din Iasi | volume = 108 | issue = 2 | pages = 409–412 | year = 2004 | pmid = 15688823 | url = https://www.revmedchir.ro/index.php/revmedchir/issue/view/72 | trans-title = Trifluridine therapy in herpetic in keratitis }} * {{cite journal | vauthors = Kuster P, Taravella M, Gelinas M, Stepp P | title = Delivery of trifluridine to human cornea and aqueous using collagen shields | journal = The CLAO Journal | volume = 24 | issue = 2 | pages = 122–124 | date = April 1998 | pmid = 9571274 }} * {{cite journal | vauthors = O'Brien WJ, Taylor JL | title = Therapeutic response of herpes simplex virus-induced corneal edema to trifluridine in combination with immunosuppressive agents | journal = Investigative Ophthalmology & Visual Science | volume = 32 | issue = 9 | pages = 2455–2461 | date = August 1991 | pmid = 1907950 }} * {{cite web | url = http://ecatalog.alcon.com/pi/Trifluridine_us_en.pdf | title = Trifluridine Ophthalmic Solution, 1% | access-date = 2007-03-24 | archive-date = 2009-09-20 | archive-url = https://web.archive.org/web/20090920002853/http://ecatalog.alcon.com/pi/Trifluridine_us_en.pdf }} {{refend}}
{{Antivirals}} {{Ophthalmological anti-infectives}}
Category:Anti-herpes virus drugs Category:Antineoplastic drugs Category:Trifluoromethyl compounds Category:Drugs developed by GSK plc Category:Drugs developed by Pfizer Category:Thymine derivatives