Idoxuridine

Idoxuridine

Clinical data
Other names	Iododeoxyuridine; IUdR
AHFS/Drugs.com	Micromedex Detailed Consumer Information
MedlinePlus	a601062
Pregnancy category	B1 (topical), B3 (ophthalmologic) [AU]
Routes of administration	topically
ATC code	D06BB01 ( WHO ) J05AB02 ( WHO ), S01AD01 ( WHO )
Legal status
Legal status	AU: S4 (Prescription only) In general: ℞ (Prescription only)
Identifiers
IUPAC name 1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-iodo-1,2,3,4-tetrahydropyrimidine-2,4-dione
CAS Number	54-42-2  Y
PubChem CID	5905
DrugBank	DB00249  Y
ChemSpider	10481938  Y
UNII	LGP81V5245
KEGG	D00342  Y
ChEMBL	ChEMBL788  N
NIAID ChemDB	001857
CompTox Dashboard (EPA)	DTXSID2045238
ECHA InfoCard	100.000.189
Chemical and physical data
Formula	C9H11IN2O5
Molar mass	354.100 g·mol−1
3D model (JSmol)	Interactive image
SMILES I\C1=C\N(C(=O)NC1=O)C2C[C@H](O)[C@@H](CO)O2
InChI InChI=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 Y Key:XQFRJNBWHJMXHO-GFCOJPQKSA-N Y
NY  (what is this?)    (verify)

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. ^[1] Initially developed as an anticancer drug, idoxuridine became the first antiviral agent in 1962. ^[2]

Clinical use

Idoxuridine is mainly used topically to treat herpes simplex keratitis. ^[3] Epithelial lesions, especially initial attacks presenting with a dendritic ulcer, are most responsive to therapy, while infection with stromal involvement are less responsive. ^[4] Idoxuridine is ineffective against herpes simplex virus type 2 and varicella-zoster. ^[3]

Side effects

Common side effects of the eye drops include irritation, blurred vision and photophobia. ^[5] Corneal clouding and damage of the corneal epithelium may also occur.^{[ citation needed ]}

Formulations and dosage

Idoxuridine is available as either a 0.5% ophthalmic ointment or as a 0.1% ophthalmic solution. ^[3] The dosage of the ointment is every 4 hours during day and once before bedtime. ^[3] 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. ^[3] Therapy is continued for 3–4 days after healing is complete, as demonstrated by fluorescein staining. ^[3]

Synthesis

Idoxuridine synthesis.

See also

• Trifluridine
• Acyclovir
• Foscarnet

References

1. Prusoff WH (March 1959). "Synthesis and biological activities of iododeoxyuridine, an analog of thymidine". Biochimica et Biophysica Acta. 32 (1): 295–296. doi: 10.1016/0006-3002(59)90597-9 . PMID   13628760.
2. Wilhelmus KR (January 2015). "Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis". The Cochrane Database of Systematic Reviews. 1 (1) CD002898. doi:10.1002/14651858.CD002898.pub5. PMC   4443501 . PMID   25879115.
3. Goodman and Gilman's The Pharmacological Basis of Therapeutics. Edited by Gilman AG, Rall TW, Nies AS, Taylor P. McGraw-Hill. 8th ed. 1990.
4. Maxwell E (October 1963). "Treatment of herpes keratitis with 5-iodo-2-deoxyuridine (IDU): a clinical evaluation of 1500 cases". American Journal of Ophthalmology. 56: 571–573. doi:10.1016/0002-9394(63)90006-0. PMID   14070708.
5. Drugs.com: Idoxuridine ophthalmic
6. FR 1336866,Gaston A, Vesperto T,"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]",published 1963-09-06, assigned to Roussel-Uclaf  
7. GB 1024156,"Process for the preparation of 5-iodo-2'-desoxy-uridine",published 1966-03-30, assigned to Roussel-Uclaf  
8. Cheong L, Rich MA, Eidinoff ML (May 1960). "Introduction of the 5-halogenated uracil moiety into deoxyribonucleic acid of mammalian cells in culture". The Journal of Biological Chemistry. 235 (5): 1441–1447. doi: 10.1016/S0021-9258(18)69427-X . PMID   13809628.
9. Chang PK, Welch AD (July 1963). "Iodination of 2'-Deoxycytidine and Related Substances". Journal of Medicinal Chemistry. 6 (4): 428–430. doi:10.1021/jm00340a019. PMID   14184899.

Further reading

• Seth AK, Misra A, Umrigar D (August 2004). "Topical liposomal gel of idoxuridine for the treatment of herpes simplex: pharmaceutical and clinical implications". Pharmaceutical Development and Technology. 9 (3): 277–289. doi:10.1081/PDT-200031432. PMID   15458233. S2CID   33864681.
• Otto SE (1998). "Radiopharmaceuticals (Strontium 89) and radiosensitizers (idoxuridine)". Journal of Intravenous Nursing. 21 (6): 335–337. PMID   10392098.
• Fauth E, Zankl H (April 1999). "Comparison of spontaneous and idoxuridine-induced micronuclei by chromosome painting". Mutation Research. 440 (2): 147–156. Bibcode:1999MRGTE.440..147F. doi:10.1016/s1383-5718(99)00021-2. PMID   10209337.