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 ;
PubChem CID	5905;
DrugBank	DB00249 ;
ChemSpider	10481938 ;
UNII	LGP81V5245;
KEGG	D00342 ;
ChEMBL	ChEMBL788 ;
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 ; Key:XQFRJNBWHJMXHO-GFCOJPQKSA-N ;
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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.

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.[1][6][7][8][9]

References

Prusoff, W. H. (1959). "Synthesis and biological activities of iododeoxyuridine, an analog of thymidine". Biochimica et Biophysica Acta. 32 (1): 295–6. doi:10.1016/0006-3002(59)90597-9. PMID 13628760.
Wilhelmus KR (2015). "Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis". Cochrane Database Syst Rev. 1: CD002898. doi:10.1002/14651858.CD002898.pub5. PMC 4443501. PMID 25879115.
Goodman and Gilman's The Pharmacological Basis of Therapeutics. Edited by Gilman AG, Rall TW, Nies AS, Taylor P. McGraw-Hill. 8th ed. 1990.
Maxwell, E (1963). "Treatment of herpes keratitis with 5-iodo-2-deoxyuridine (IDU): a clinical evaluation of 1500 cases". Am. J. Ophthalmol. 56: 571–573. doi:10.1016/0002-9394(63)90006-0. PMID 14070708.
Drugs.com: Idoxuridine ophthalmic
FR 1336866, Gaston, Amiard & Vesperto, Torelli, "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
GB 1024156, "Process for the preparation of 5-iodo-2'-desoxy-uridine", published 1966-03-30, assigned to Roussel-Uclaf
Cheong, L.; Rich, M. A.; Eidinoff, M. L. (1960). "Introduction of the 5-Halogenated Uracil Moiety into Deoxyribonucleic Acid of Mammalian Cells in Culture". J. Biol. Chem. 235 (5): 1441–1447. doi:10.1016/S0021-9258(18)69427-X. PMID 13809628.
Chang, P. K.; Welch, A. D. (1963). "Iodination of 2'-Deoxycytidine and Related Substances1". Journal of Medicinal Chemistry. 6 (4): 428–430. doi:10.1021/jm00340a019. PMID 14184899.