Idoxuridine

Idoxuridine

A systematic review and meta-analysis to compare the efficacy of acyclovir 3% ophthalmic ointment to idoxuridine in curing herpetic keratitis by Day 7 of treatment.[Pubmed:25928630]

BMC Ophthalmol. 2015 Apr 17;15:42.

BACKGROUND: This objective of the review and analysis is to demonstrate that acyclovir (ACV) 3% ophthalmic ointment is superior to Idoxuridine (IDU) in treating herpetic keratitis (HK) presenting as dendritic and geographic ulcer sub-types. METHODS: DATA SOURCES: Publications in human subjects were identified by searching the Ovid MEDLINE database through April 2011, combining medical subject headings (MESH) "Keratitis, Herpetic/" AND "Acyclovir/" limiting by the key words "topical" OR "ointment" and also restricted to MESH "Administration, Topical/" OR "Ointments/". The results were cross checked with the references used in the Cochrane Database Syst Rev. 1:1-134, 2009 and GlaxoSmithKline clinical documents related to acyclovir. STUDY SELECTION: Randomized, double-masked studies in subjects diagnosed with HK with head to head comparator arms of ACV ophthalmic ointment and topical IDU that had actual or calculable healing rates at Day seven. DATA EXTRACTION: Data independently extracted from identified articles by two authors of this manuscript. DATA SYNTHESIS: Data from seven randomized, controlled trials (RCT) evaluating 432 subjects that met inclusion criteria (214 were treated with ACV and 218 were treated with IDU) and had Day seven healing rates calculable. All sub-classified lesions were identified as either dendritic ulcers (n = 185) or geographic ulcers (n = 35). The Cochran-Mantel-Haenszel (CMH) method in Biometrics 10:417-51, 1954 and JNCI 22:719-48, 1959, controlling for study, was performed as the primary analysis using SAS v9. Homogeneity was assessed using Breslow-Day-Tarone (BDT) test in IARC 1:1-32, 1980 and Biometrika 72:91-5, 1985. The analysis was performed with outliers removed to assess their impact. RESULTS: ACV showed statistically significant greater odds of healing HK at Day seven in all subjects (Odds Ratio 3.95, 95% CI2.60, 6.00, p < 0.0001), in dendritic ulcers (Odds Ratio 4.22, 95% CI: 2.14, 8.32; p < 0.0001) and geographic ulcers (Odds Ratio 5.31, 95% CI: 1.09, 25.93; p = 0.0244). CONCLUSION: ACV 3% ophthalmic ointment is a valuable intervention for dendritic and geographic corneal ulcers. ACV and IDU were generally well tolerated in the studies reviewed.

In vitro efficacy of ganciclovir, cidofovir, penciclovir, foscarnet, idoxuridine, and acyclovir against feline herpesvirus type-1.[Pubmed:15077679]

Am J Vet Res. 2004 Apr;65(4):399-403.

OBJECTIVE: To establish the in vitro efficacy of 4 novel drugs (ie, ganciclovir, cidofovir, penciclovir, and foscarnet) against feline herpesvirus type-1 (FHV-1) and compare their antiviral efficacy with that of acyclovir and Idoxuridine. SAMPLE POPULATION: Cultured Crandell-Reese feline kidney (CRFK) cells and FHV-1 strain 727 PROCEDURE: For each drug, antiviral effect was estimated by use of conventional plaque-reduction assays, and inhibitory concentration 50 (IC50; drug concentration at which plaque numbers were reduced by 50% relative to the number of plaques for nontreated control wells) was calculated. To determine whether observed antiviral effects were related to alterations in the number or viability of CRFK cells, cytotoxicity assays were performed at 1, 2, and 10 times the median IC50 for each antiviral drug. RESULTS: Median IC50 for each drug was as follows: ganciclovir, 5.2 microM; cidofovir, 11.0 microM; penciclovir, 13.9 microM; foscarnet, 232.9 microM; Idoxuridine, 4.3 microM; and acyclovir, 57.9 microM. Obvious changes in morphologic characteristics, confluence, or viability of CRFK cells were not observed at concentrations up to and including 2 times the IC50 for each drug. CONCLUSIONS AND CLINICAL RELEVANCE: In vitro efficacy of Idoxuridine and ganciclovir against FHV-1 was approximately equivalent and about twice that of cidofovir and penciclovir. Foscarnet appeared to be comparatively ineffective. Given the reasonable clinical efficacy of Idoxuridine in cats infected with FHV-1, clinical trials of ganciclovir, cidofovir, and penciclovir or their prodrug forms appear to be warranted.

Synergistic combination effect of cidofovir and idoxuridine on vaccinia virus replication.[Pubmed:17042327]

Antivir Chem Chemother. 2006;17(2):53-8.

In view of the potential menace of a terrorism attack with smallpox virus, an intensive search of chemotherapeutic agents active against orthopoxviruses is underway. We comparatively studied the antiviral activity of cidofovir (CDV) and Idoxuridine (IUdR) against two vaccinia virus (VV) strains, Bratislava and RIIPD, in cell cultures of chick embryo fibroblasts (CEF). The investigations were carried out according to cytopathic effect (CPE) inhibition assay protocols. To determine the cytotoxicity of the compounds, maximal tolerated concentration (MTC) was calculated in CEF cell monolayers and 50% cell growth inhibitory concentration (CGIC50) was calculated in growing cell cultures. It was found that the antiviral effects were strongly dependent on virus inoculum size. There were no marked differences in the susceptibility to CDV and IUdR between the two VV strains. The individual half maximal inhibitory concentration (IC50) for CDV varied from 7.1-8.5 microM at 10/100 virus 50% infectious dose (ID50) to 13.6-26.5 microM at 10,000 ID50. The CDV selectivity index was also virus dose-dependent with MTC/IC50 and CGIC50/IC50 values ranging between 37.8-141.4 and 33.3-124.6, respectively. For IUdR, IC50 ranged from 0.58 to 0.85 microM, but the selectivity index for monolayer CEF and growing cell cultures produced substantial different results with MTC/IC50 and CGIC50/IC50 values between 117.7-172.4 and 20.4-33.3, respectively. The combination effects of CDV and IUdR against VV Bratislava strain in the CPE inhibition test were also determined. The test design of both combination antiviral effect and combined cytotoxicity followed a three-dimensional model. The combined effect of CDV and IUdR on VV replication in monolayer CEF cultures was characterized as a markedly synergistic one. In contrast, CDV and IUdR together reduced cytotoxicity in both monolayer and growing CEF cells.

Topical liposomal gel of idoxuridine for the treatment of herpes simplex: pharmaceutical and clinical implications.[Pubmed:15458233]

Pharm Dev Technol. 2004 Aug;9(3):277-89.

The optimization of the method of preparation of Idoxuridine (IDU) liposomes by the reverse phase evaporation (REV) method was carried out by three variables at three levels (3(3)) factorial design. The three independent variables selected were volume of organic phase (x1), volume of aqueous phase (x2), and drug/phosphatidylcholine/cholesterol in molar ratio (x3). Twenty-seven batches of IDU liposomes were prepared by the REV method and subjected to evaluation for percentage drug entrapment (PDE), size, and size distribution. A reduced polynomial equation was derived by multiple regression of the data of PDE and the transformed values of the three independent variables. Three contour plots at fixed level of-- 1 (low), 0 (medium), and 1 (high) of major contributing variable (x3) were plotted between x1 and x2 at predetermined PDE to understand the physical meaning of independent variables. Liposomal gels were prepared by dispersing optimized IDU liposomes in 2%w/w and 5%w/w (HPMC) K4M gel bases so as to contain 1%w/w IDU (LIG-1 and LIG-2, respectively). The percentage of drug retention (PDR) studies of optimized batch 14 (Lipo-14) and LIG-1 and LIG-2 were carried out at three different storage conditions (2-8 degrees C, 25 +/- 2 degrees C, and 37 degrees C). A comparative diffusion study of LIG-1 and LIG-2 with PIG-1 and PIG-2 (1%w/w IDU with components of liposome dispersed in 2%w/w and 5%w/w HPMC K4M gel bases, respectively), respectively, through human cadaver skin was conducted. A comparative double blind clinical pilot study of optimized LIG-2 gel was carried out for eight weeks and compared with PIG-2 on 20 Herpes simplex patients (10 patients each for HSV-1 and HSV-2, divided into two groups each of 5 patients). Batch 14 (Lipo-14) was found to have maximum PDE of 74.4%. The PDR study showed maximum drug retention at 2-8 degrees C. A significant increase in PDR (p<0.05) was observed in LIG-1 and LIG-2 when compared with Lipo-14 at all the three temperatures. In the diffusion studies, a significant (p<0.05) flux reduction; 3.5 times in LIG-1 when compared with PIG-1 and 2.3 times in LIG-2 when compared with PIG-2 was observed. Approximately 2.2- and 2.5-fold increase in skin drug retention in LIG-1 and LIG-2, respectively, was determined. A double blind clinical study demonstrated an approximately 2.0- and 1.6-fold increase in average percentage improvement in healing of the lesions in patients suffering from HSV-1 and HSV-2 diseases, respectively, when treated with LIG-2 compared with PIG-2. However, complete removal of lesions was not observed. Local side effects such as itching, burning, inflammation in HSV-1 and HSV-2, and burning micturation in HSV-2 associated with the use of PIG-2 were reduced considerably with the use of LIG-2. The findings of this investigation establish the role of the derived equation and plotted contour plots in predicting the values of independent variables for preparation of IDU liposomes by the REV method. The study also demonstrated that IDU liposomal gels retain more drug when compared with plain liposomes at all temperatures for the period of three months, while maximum PDR was found at refrigeration temperature. The skin retention of IDU was enhanced due to its entrapment in the liposomal vesicles. The clinical study suggested the improvement of therapeutic efficacy of IDU entrapped in liposomes in treatment of HSV-1 and HSV-2 patients.