Idoxuridine (2-10 μM, 72 hours) possesses an IC50 value of 4.3 μM, making it an antiviral medication [1].

Idoxuridine stimulates C3HeB/FeJ female and male mice as well as A/J female mice when administered intraperitoneally three times, three hours apart, at a dose of 50–200 mg/kg [2].

Cell proliferation assay [1]
Cell Types: Crandell-Reese cat kidney (CRFK) Cell
Tested Concentrations: 2-10 μM
Incubation Duration: 72 hrs (hours)
Experimental Results: Shows IC50 value of 4.3μM.

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Cytotoxicity assay [1]
Cell Types: Crandell-Reese cat kidney (CRFK) cell
Tested Concentrations: 5-50 μM
Incubation Duration: 72 hrs (hours)
Experimental Results: 10.8% reduction relative to CRFK cells.

Animal/Disease Models: C3HeB/FeJ female and male mice and A/J male mice, 2 to 4 months old [2]
Doses: 50-200 mg/kg
Route of Administration: intraperitoneal (ip) injection, 3 times, 3 hrs (hrs (hours)) apart.
Experimental Results: The dose range for stimulating the production of red blood cells (SRBC) by sheep hemolysin plaque forming cells (HPFC) is 50-200 mg/kg.

Absorption, Distribution and Excretion
Systemic absorption is unlikely following ocular administration even when nasolacrimal secretions are swallowed, since vidarabine is rapidly deaminated in the gastrointestinal tract.
Idoxuridine penetrates the cornea poorly and therefore is ineffective in the treatment of iritis or deep stromal infections.
Idoxuridine crosses the placenta. Studies in humans have not been done.
It is not known whether idoxuridine is distributed into breast milk. However, problems in humans have not been documented.
A reproducible microbiologic assay of microgram quantities of idoxuridine (IDU) in serum, urine, or cerebrospinal fluid is presented. The antiviral assay is not interfered with by type-specific antibody or interferon. During slow intravenous infusions of idox-uridine (4 mg/min) in patients with suspected diagnoses of Herpesvirus hominis encephalitis, the rate of inactivation and/or removal of drug exceeded its administration. During several rapid infusions of idoxuridine (50 mg/min) significant quantities of the drug were found in serum, urine, and cerebrospinal fluid. Idoxuridine is not significantly bound to serum proteins and is not deiodinated in fresh serum or urine in vitro to inactive products (iodouracil, uracil, iodide). It is rapidly excreted into the urine. Inactivation of IDU occurs in tissues. This antiviral assay of IDU in body fluids should be applicable to other viruses and potential antiviral agents.

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Metabolism / Metabolites
Idoxuridine is rapidly inactivated by deaminases or nucleotidases.
Idoxuridine is rapidly inactivated by deaminases or nucleotidases.

Toxicity Data
Rat(ip): LD50: 4000 mg/kg
Mouse(ip): LD50: 1000 mg/kg

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Interactions
Concurrent use of boric acid with idoxuridine formulations is not recommended; boric acid may interact with inactive ingredients in some idoxuridine formulations, resulting in precipitate formation; in addition, boric acid may interact with preservatives, especially higher concentrations of thimerosal, in other idoxuridine formulations, resulting in increased ocular toxicity.

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Non-Human Toxicity Values
LD50 Mouse ip 2.5 g/kg

[1]. In vitro efficacy of ganciclovir, cidofovir, penciclovir, foscarnet, idoxuridine, and acyclovir against feline herpesvirus type-1. Am J Vet Res. 2004 Apr;65(4):399-403.

[2]. Stimulation of hemolysin plaque-forming cells by idoxuridine. Cancer Res. 1975 Jan;35(1):88-92.

[3]. Orthopoxvirus targets for the development of antiviral therapies. Curr Drug Targets Infect Disord.

5-iodo-2'-deoxyuridine is a pyrimidine 2'-deoxyribonucleoside compound having 5-iodouracil as the nucleobase; used as an antiviral agent. It has a role as an antiviral drug and a DNA synthesis inhibitor. It is a pyrimidine 2'-deoxyribonucleoside and an organoiodine compound.
An analog of deoxyuridine that inhibits viral DNA synthesis. The drug is used as an antiviral agent.
Idoxuridine is a Nucleoside Analog Antiviral.
Idoxuridine is an iodinated analogue of deoxyuridine, with antiviral activity against herpes simplex virus (HSV) and potential radiosensitizing activities. Upon ocular administration, idoxuridine (IUdR) is converted to its mono-, di-, and triphosphate forms, is incorporated into DNA and disrupts viral replication. Upon oral administration of the idoxuridine prodrug ropidoxuridine and hepatic conversion by aldehyde oxidase into idoxuridine, this agent incorporates into DNA and sensitizes cells to ionizing radiation by increasing DNA strand breaks.
An analog of DEOXYURIDINE that inhibits viral DNA synthesis. The drug is used as an antiviral agent.

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Drug Indication
For use in keratoconjunctivitis and keratitis caused by herpes simplex virus.

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Mechanism of Action
Idoxuridine acts as an antiviral agent by inhibiting viral replication by substituting itself for thymidine in viral DNA. This in turn inhibits thymidylate phosphorylase and viral DNA polymerases from properly functioning. The effect of Idoxuridine results in the inability of the virus to reproduce or to infect/destroy tissue.
Idoxuridine, which closely resembles thymidine, inhibits thymidylic phosphorylase and specific DNA polymerases, which are necessary for the incorporation of thymidine into viral DNA. Idoxuridine is incorporated in place of thymidine into viral DNA, resulting in faulty DNA and the inability to infect or destroy tissue or to reproduce. Idoxuridine is incorporated into mammalian DNA as well.

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Therapeutic Uses
Antiviral
Idoxuridine is indicated in the treatment of keratitis caused by herpes simplex virus (HSV). /Included in US product label/
Idoxuridine is indicated in the treatment of keratitis caused by vaccinia virus. /Not included in US product label/
Idoxuridine is used in the treatment of keratoconjunctivitis caused by herpes simplex virus (HSV). /Not included in US product label/
Idoxuridine has no effect on accumulated scarring, vascularization, or progressive loss of vision that may result from the infection. It also has no effect on corneal inflammation that may follow HSV keratitis when the virus is absent, nor on adenoviral keratoconjunctivitis. /Not included in US product label/

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Drug Warnings
Patients sensitive to iodine or iodine-containing preparations may be sensitive to this medication also.
The following side/adverse effects have been selected on the basis of their potential clinical significance: Incidence less frequent /include/ Hypersensitivity (itching, redness, swelling, pain, or other sign of irritation not present before therapy), or increased sensitivity of eyes to light; Incidence rare: Corneal clouding (blurring, dimming, or haziness of vision).
FDA Pregnancy Risk Category: C /RISK CANNOT BE RULED OUT. Adequate, well controlled human studies are lacking, and animal studies have shown risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is given during pregnancy; but the potential benefits may outweigh the potential risk./
The ... toxicity of topical applications of 30% idoxuridine in dimethyl sulfoxide, dimethyl sulfoxide alone, or saline in 96 recurrent and 39 first episodes of genital herpes simplex virus (HSV) infection were compared. ...Complications in patients given idoxuridine in dimethyl sulfoxide included local burning, generalized contact dermatitis, and vulvar carcinoma in situ. Thirty percent idoxuridine in dimethyl sulfoxide has no effect on clinical manifestations of genital HSV infection and may be hazardous.

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Pharmacodynamics
In chemical structure idoxuridine closely approximates the configuration of thymidine, one of the four building blocks of DNA (the genetic material of the Herpes virus). As a result, idoxuridine is able to replace thymidine in the enzymatic step of viral replication or "growth". The consequent production of faulty DNA results in a pseudostructure which cannot infect or destroy tissue. In short, by pre-empting a vital building block in the genetic material of the Herpes simplex virus, Herplex-D topical solution destroys the infective and destructive capacity of the viral material. The virus infected cell may only be attacked during the period of active synthesis of DNA. This occurs early in the development of the Herpes simplex lesion, but at different times in different cells. Therefore, ideally, the affected area should remain saturated with the antiviral agent.

C9H11IN2O5

354.0985

353.971

54-42-2

Idoxuridine hydrate;17140-71-5

5905

White to off-white solid powder

2.1±0.1 g/cm3

194 °C(lit.)

1.715

-0.52

3

5

2

17

386

3

C1[C@@H]([C@H](O[C@H]1N2C=C(C(=O)NC2=O)I)CO)O

XQFRJNBWHJMXHO-RRKCRQDMSA-N

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

1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-iodopyrimidine-2,4-dione

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~125 mg/mL (~353.01 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.87 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (5.87 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (5.87 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)