{{short description|Chemical compound}} {{Drugbox | Verifiedfields = changed | verifiedrevid = 461936439 | IUPAC_name = 1-[(2''R'',4''S'',5''R'')-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-iodo-1,2,3,4-tetrahydropyrimidine-2,4-dione | image = Idoxuridine - Idoxuridin.svg | image_class = skin-invert-image | width = 200 <!--Clinical data--> | tradename = | Drugs.com = {{drugs.com|CONS|idoxuridine}} | MedlinePlus = a601062 | pregnancy_category = B1 (topical), B3 (ophthalmologic) [AU] | pregnancy_US = C | legal_AU = S4 | legal_UK = <!-- GSL / P / POM / CD --> | legal_US = <!-- OTC / Rx-only --> | legal_status = Rx-only | routes_of_administration = topically <!--Pharmacokinetic data--> | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion = <!--Identifiers--> | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 54-42-2 | ATC_prefix = D06 | ATC_suffix = BB01 | ATC_supplemental = {{ATC|J05|AB02}}, {{ATC|S01|AD01}} | PubChem = 5905 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00249 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 10481938 | NIAID_ChemDB = 001857 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = LGP81V5245 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00342 | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 788 <!--Chemical data--> | C=9 | H=11 | I=1 | N=2 | O=5 | smiles = I\C1=C\N(C(=O)NC1=O)C2C[C@H](O)[C@@H](CO)O2 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C9H11IN2O5/c10-4-2-12(9(16)11-8(4)15)7-1-5(14)6(3-13)17-7/h2,5-7,13-14H,1,3H2,(H,11,15,16)/t5-,6+,7?/m0/s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = XQFRJNBWHJMXHO-GFCOJPQKSA-N | synonyms = Iododeoxyuridine; IUdR }} '''Idoxuridine''' is an anti-herpesvirus antiviral drug.
It is a nucleoside analogue, a modified form of deoxyuridine, similar enough to be incorporated into viral DNA replication, but the iodine atom added to the uracil component blocks base pairing. It is used only topically due to cardiotoxicity. It was synthesized by William Prusoff in the late 1950s.<ref name=Prusoff /> Initially developed as an anticancer drug, idoxuridine became the first antiviral agent in 1962.<ref name="Wilhelmus">{{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>
==Clinical use== Idoxuridine is mainly used topically to treat herpes simplex keratitis.<ref name="Goodman">Goodman and Gilman's The Pharmacological Basis of Therapeutics. Edited by Gilman AG, Rall TW, Nies AS, Taylor P. McGraw-Hill. 8th ed. 1990.</ref> Epithelial lesions, especially initial attacks presenting with a dendritic ulcer, are most responsive to therapy, while infection with stromal involvement are less responsive.<ref>{{cite journal | vauthors = Maxwell E | title = Treatment of herpes keratitis with 5-iodo-2-deoxyuridine (IDU): a clinical evaluation of 1500 cases | journal = American Journal of Ophthalmology | volume = 56 | pages = 571–573 | date = October 1963 | pmid = 14070708 | doi = 10.1016/0002-9394(63)90006-0 }}</ref> Idoxuridine is ineffective against herpes simplex virus type 2 and varicella-zoster.<ref name="Goodman"/>
==Side effects== Common side effects of the eye drops include irritation, blurred vision and photophobia.<ref>Drugs.com: [https://www.drugs.com/mtm/idoxuridine-ophthalmic.html Idoxuridine ophthalmic]</ref> Corneal clouding and damage of the corneal epithelium may also occur.{{citation needed|date=February 2012}}
==Formulations and dosage== Idoxuridine is available as either a 0.5% ophthalmic ointment or as a 0.1% ophthalmic solution.<ref name="Goodman"/> The dosage of the ointment is every 4 hours during day and once before bedtime.<ref name="Goodman"/> The dosage of the solution is 1 drop in the conjunctival sac hourly during the day and every 2 hours during the night until definitive improvement, then 1 drop every 2 hours during the day and every 4 hours during the night.<ref name="Goodman"/> Therapy is continued for 3–4 days after healing is complete, as demonstrated by fluorescein staining.<ref name="Goodman"/>
==Synthesis== [[File:Idoxuridine synthesis.svg|thumb|center|500px|Idoxuridine synthesis.<ref name=Prusoff>{{cite journal | vauthors = Prusoff WH | title = Synthesis and biological activities of iododeoxyuridine, an analog of thymidine | journal = Biochimica et Biophysica Acta | volume = 32 | issue = 1 | pages = 295–296 | date = March 1959 | pmid = 13628760 | doi = 10.1016/0006-3002(59)90597-9 | doi-access = free }}</ref><ref>{{Cite patent|country=FR|number=1336866|pubdate=1963-09-06|title=Nouveau procédé de préparation d'un dérivé de l'uridine et produits utilisés dans ce procédé [New process for preparing a derivative of uridine and products used in this process]|assign1=Roussel-Uclaf|inventor = Gaston A, Vesperto T }}</ref><ref>{{Cite patent|country=GB|number=1024156|pubdate=1966-03-30|title=Process for the preparation of 5-iodo-2'-desoxy-uridine|assign1=Roussel-Uclaf}}</ref><ref>{{cite journal | vauthors = Cheong L, Rich MA, Eidinoff ML | title = Introduction of the 5-halogenated uracil moiety into deoxyribonucleic acid of mammalian cells in culture | journal = The Journal of Biological Chemistry | volume = 235 | issue = 5 | pages = 1441–1447 | date = May 1960 | pmid = 13809628 | doi = 10.1016/S0021-9258(18)69427-X | doi-access = free }}</ref><ref>{{cite journal | vauthors = Chang PK, Welch AD | title = Iodination of 2'-Deoxycytidine and Related Substances | journal = Journal of Medicinal Chemistry | volume = 6 | issue = 4 | pages = 428–430 | date = July 1963 | pmid = 14184899 | doi = 10.1021/jm00340a019 }}</ref>]]
== See also == * Trifluridine * Acyclovir * Foscarnet
== References == {{reflist}}
== Further reading == {{refbegin}} * {{cite journal | vauthors = Seth AK, Misra A, Umrigar D | title = Topical liposomal gel of idoxuridine for the treatment of herpes simplex: pharmaceutical and clinical implications | journal = Pharmaceutical Development and Technology | volume = 9 | issue = 3 | pages = 277–289 | date = August 2004 | pmid = 15458233 | doi = 10.1081/PDT-200031432 | s2cid = 33864681 }} * {{cite journal | vauthors = Otto SE | title = Radiopharmaceuticals (Strontium 89) and radiosensitizers (idoxuridine) | journal = Journal of Intravenous Nursing | volume = 21 | issue = 6 | pages = 335–337 | year = 1998 | pmid = 10392098 }} * {{cite journal | vauthors = Fauth E, Zankl H | title = Comparison of spontaneous and idoxuridine-induced micronuclei by chromosome painting | journal = Mutation Research | volume = 440 | issue = 2 | pages = 147–156 | date = April 1999 | pmid = 10209337 | doi = 10.1016/s1383-5718(99)00021-2 | bibcode = 1999MRGTE.440..147F }} {{refend}} <!-- Discovered in 1950 -->
{{Antibiotics and chemotherapeutics for dermatological use}} {{Antivirals}} {{Ophthalmological anti-infectives}}
Category:Nucleosides Category:Uracil derivatives Category:Organoiodides Category:Anti-herpes virus drugs Category:Hydroxymethyl compounds