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At least 19 recordsLinked to original sources
PubMed1998

Trifluridine, cidofovir, and penciclovir in the treatment of experimental herpetic keratitis.

OBJECTIVE: To compare trifluridine eyedrops, cidofovir eyedrops, and penciclovir ophthalmic ointment for the treatment of herpes simplex virus type 1 keratitis. METHODS: New Zealand white rabbits were infected with the McKrae strain of herpes simplex virus type 1. Three days after viral inoculation, the rabbits were randomly assigned to treatment with 1% trifluridine, 0.2% cidofovir, 3% penciclovir ointment, or phosphate-buffered saline (for control) on various schedules. The severity of keratitis was graded in a masked manner. RESULTS: Treatment with any of the antiviral drugs resulted in significantly less severe keratitis than treatment with phosphate-buffered saline. There was no statistically significant difference between eyes given trifluridine 2, 4, or 7 times a day and eyes given cidofovir 2 times a day (P=.06, P=.43, and P=.19, respectively, using the F test of the analysis of variance). Cidofovir given twice a day was significantly more effective than penciclovir given either 2 or 4 times a day (P<.001 and P=.002, respectively). Even with once-a-day dosage, all 3 drugs were significantly more effective than phosphate-buffered saline (P<.001 for all). There was no significant difference between once-a-day trifluridine and cidofovir treatments (P=.17). Trifluridine administered 5 times a day was as effective as 1% cidofovir. A similar degree of punctate keratitis was seen after 4 to 5 days in eyes treated with trifluridine at the highest frequency, 1% cidofovir, or penciclovir ointment. CONCLUSION: Trifluridine treatment was highly effective in this rabbit model, even when given only once a day. Treatment with cidofovir was as effective as that with trifluridine. CLINICAL RELEVANCE: Cidofovir and penciclovir treatments may prove to be effective against epithelial keratitis. Clinical trials of trifluridine, cidofovir, and penciclovir with lower treatment frequencies appear to be warranted.

Acyclovir↗
PubMed1982

Experimental stroma herpes simplex keratitis. Influence of treatment with topical bromovinyldeoxyuridine and trifluridine.

Two compounds, bromovinyldeoxyuridine ([E]-5-[2-bromovinyl]-2'-deoxyuridine) and trifluridine (5-trifluoromethyl-2' deoxyuridine) were compared for their efficacy in the topical treatment of experimental stroma herpetic keratitis produced by the injection of live herpes simplex virus, type 1, into the corneal stroma of rabbits. The trifluridine was used as 1% eyedrops, whereas bromovinyldeoxyuridine was used as either 0.1% or 0.5% eyedrops. All three treatment regimens caused a substantial healing of stroma disease in comparison with placebo treatment. The bromovinyldeoxyuridine (whether used as 0.1% or 0.5%) proved superior to 1% trifluridine eyedrops when the treatment was started one day after virus inoculation. However, bromovinyldeoxyuridine and trifluridine were equally effective if the treatment was started seven days after infection. The 0.5% bromovinyldeoxyuridine eyedrops seemed to be more effective in controlling the complicating severe iritis and secondary glaucoma than either 0.1% bromovinyldeoxyuridine or 1% trifluridine. No toxic effects were observed with bromovinyldeoxyuridine in any eye, whereas 1% trifluridine produced punctate epitheliopathy in some eyes.

Animals↗
PubMed1985

Role of débridement and trifluridine (trifluorothymidine) in herpes simplex dendritic keratitis.

Thirty-four patients with herpes simplex dendritic keratitis were randomized into three treatment categories: Group A had débridement alone; group B, trifluridine (trifluorothymidine) alone; and group C, débridement and trifluridine. Patients treated with débridement alone had a statistically higher failure rate than did the other two groups. No statistically significant difference was observed between trifluridine treatment alone and débridement combined with trifluridine treatment, with regard to healing time. Our results suggest that débridement alone is suboptimal therapy for herpes simplex dendritic keratitis and that débridement combined with trifluridine appears to offer no advantage over trifluridine alone.

Adolescent↗
PubMed1979

Intraocular penetration of trifluridine.

We studied intraocular penetration of topically applied trifluridine in five patients with herpetic keratitis undergoing penetrating keratoplasty. We compared the concentration of trifluridine and its metabolite 5-carboxy 2'-deoxyuridine in the aqueous humor to those of normal control patients undergoing routine cataract extraction without preoperative antiviral therapy. Significant concentrations of intact trifluridine were achieved in the acqueous humor after topical application of 1% trifluridine ophthalmic drops. The metabolite, 5-carboxy 2'-deoxyuridine, was not found in the aqueous humor. Unlike idoxuridine and vidarabine, it is possible to achieve therapeutic levels of trifluridine at intraocular sites that would be advantageous in the treatment of deep herpetic disease involving the stroma and iris.

Aqueous Humor↗
PubMed1996

Pilot study of topical trifluridine for the treatment of acyclovir-resistant mucocutaneous herpes simplex disease in patients with AIDS (ACTG 172). AIDS Clinical Trials Group.

SUMMARY: Twenty-six AIDS patients were enrolled in an open label pilot study to evaluate the efficacy and toxicity of topical 1 percent ophthalmic trifluridine solution for the treatment of chronic mucocutaneous herpes simplex virus disease unresponsive to at least 10 days of acyclovir therapy. Susceptibility testing to acyclovir, trifluridine, and foscarnet was determined by plaque reduction assay. Twenty-four patients were evaluable for efficacy and 25 for toxicity analyses. Seven patients (29 percent) had complete healing of lesions. The overall estimated median time to complete healing was 7.1 weeks. An additional seven patients had > or = 50 percent reduction in lesion area. The overall estimated median time to 50 percent healing was 2.4 weeks. Ten (42 percent) patients discontinued treatment for reasons other than primary treatment failure and seven (29 percent) for failure to respond to therapy. Baseline patient characteristics associated with greater reduction in lesion area included higher Karnofsky score (p = 0.05), fewer lesions (p = 0.07), smaller lesion area (p = 0.11), and trifluridine susceptibility (p = 0.07). Eight (33 percent) patients developed new lesions outside of the treatment area while on study, reflecting the local nature of this therapy. No dose-limiting toxicity attributable to trifluridine was reported. Given the limited options for the treatment of acyclovir-resistant herpes simplex disease, topical trifluridine may be a useful alternative in selected patients.

AIDS-Related Opportunistic Infections↗
PubMed1982

Trifluridine: a review of its antiviral activity and therapeutic use in the topical treatment of viral eye infections.

Trifluridine (trifluorothymidine) is an antiviral agent for topical use in the eye, and is structurally related to idoxuridine. In vitro studies have shown that it effectively inhibits the replication of herpes simplex virus type 1, which causes primary keratoconjunctivitis and recurrent epithelial keratitis in man. In masked comparative studies, predominantly in patients with dendritic ulcers, trifluridine 1% solution was effective in over 90% of patients; in such studies it was comparable with vidarabine in treating dendritic ulcers, and was at least as effective as, and in some studies more effective than, idoxuridine. The drug was also effective in treating a small number of patients with geographic ulcers (sometimes associated with the usage of topical corticosteroids), and this could be an important advantage if confirmed in further well-designed studies. However, experience at present is too limited to reliably determine the usual response rate in this difficult therapeutic area. In open studies the drug proved to be particularly useful in treating ulcers previously unresponsive to idoxuridine or vidarabine, and in treating patients intolerant of idoxuridine, with a high success rate and minimal side effects being reported. The role of trifluridine in treating deep stromal disease, uveitis, or adenovirus kerato-conjunctivitis has not been established. The drug is well tolerated and cross-hypersensitivity and cross-toxicity between trifluridine, idoxuridine and vidarabine are rare. Thus, trifluridine is an effective alternative to the drugs available for treating herpetic keratitis, and seems especially useful in 'difficult' cases.

Adenoviridae Infections↗
PubMed1984

Effect of topical trifluridine on Thygeson's superficial punctate keratitis.

Six eyes of four patients with Thygeson's superficial punctate keratitis were treated with trifluridine 1% drops. Five of the six treated eyes responded favorably to topical trifluridine therapy. Symptoms and later the signs of the disease disappeared, but more slowly than observed following topical corticosteroid therapy. One patient with an 11-year history of topical corticosteroid dependence for clearing of lesions was treated successfully with trifluridine, and his eyes have remained clear for over one year without therapy. Mild irritation and transient limbal follicle formation were the only recognized side effects. Trifluridine is thus an effective and safe alternative to corticosteroids in the treatment of this condition and may offer a means of treating the steroid-dependent patient.

Adult↗
PubMed1986

Efficacy of glycoprotein inhibitors alone and in combination with trifluridine in the treatment of murine herpetic keratitis.

The present study examined the anti-herpetic effect of the glycoprotein inhibitors, hydroxynorvaline and 2-deoxyglucose, alone and in combination with trifluridine on murine ocular herpes. Following ocular inoculation with a large dose of HSV-1 RE strain (10(6) pfu), ICR mice were treated during the acute infection with different therapeutic regimens, and their efficacy was evaluated by ocular virus titers, clinical grading of blepharo-conjunctivitis and histological evaluation of stromal keratitis and iridocyclitis. The results following a large dose HSV-1 inoculum demonstrated that trifluridine was the best single therapeutic agent. Hydroxynorvaline and 2-deoxyglucose had no effect at all. Combination therapy of the glycoprotein inhibitors with trifluridine was no better than trifluridine alone. The mouse HSV-1 keratitis model proved to be an effective, economical alternative to the rabbit model for the evaluation of new antiviral agents.

Animals↗
PubMed1999

Comparative antiviral efficacies of cidofovir, trifluridine, and acyclovir in the HSV-1 rabbit keratitis model.

PURPOSE: To determine the relative antiviral inhibitory activity of topical 1% and 0.5% cidofovir, topical trifluridine (Viroptic; Burroughs-Wellcome, Research Triangle Park, NC), and topical acyclovir (Zovirax; The Wellcome Foundation, London, UK) during a 7-day period for the treatment of herpes simplex virus type 1 (HSV-1) keratitis and HSV-1 replication in the New Zealand rabbit ocular model. METHODS: In a series of four experiments using a two-eye design, a total of 80 New Zealand rabbits were inoculated in both eyes with HSV-1 McKrae after epithelial scarification. Forty-eight hours after inoculation, the rabbits were randomly assigned to a treatment group. Five treatment groups (16 rabbits/group) were evaluated: I, 1% cidofovir, twice daily for 7 days; II, 0.5% cidofovir, twice daily for 7 days; III, 3% acyclovir ointment, five times daily for 7 days; IV, 1% trifluridine, nine times daily for 3 days, then 4 times daily for 4 days; and V, control vehicle twice daily for 7 days. HSV-1 dendritic keratitis was graded in a masked fashion by slit-lamp examination on days 2, 3, 5, 7, 9, 11, and 14. Ocular viral cultures were obtained after slit-lamp examination on days 1, 3, 5, 7, 9, 11, and 14. RESULTS: Compared with the control group, all four treatment groups demonstrated significantly lower viral titers, fewer HSV-1-positive eyes/total during the treatment period, lower keratitis scores, fewer eyes with keratitis/total, and a shorter time to resolution of keratitis. Within the treatment groups, the 1% and 0.5% cidofovir treatments were significantly more effective than acyclovir and trifluridine as measured by the previous viral and keratitis parameters. CONCLUSIONS: Topical 1% and 0.5% cidofovir both appeared to be significantly more efficacious than topical trifluridine and acyclovir, during a 7-day course, in the treatment of experimental HSV-1 ocular disease in the New Zealand rabbit keratitis model.

Acyclovir↗
PubMed1983

Corneal epithelial dysplasia after trifluridine use.

Prolonged topical trifluridine treatment of herpes simplex keratitis in three elderly patients produced slightly raised dysplastic corneal epithelial lesions. The involved epithelium had a ground-glass appearance and exhibited opaque cells, edema, and spindle-shaped surface cells. Histopathology demonstrated severe cellular atypism, loss of cell polarity, dyskeratosis, parakeratosis, and a few mitotic figures. The pathological change was apparently intraepithelial. After scraping, the edema and opaque cells in the regenerated epithelium gradually disappeared in 3-4 months on cessation of trifluridine therapy. In one patient recurrence of dendritic keratitis, 5 weeks after scraping, was treated by topical bromovinyldeoxyuridine eye drops. Since severe epithelial dysplasia may represent a precancerous condition, prolonged use of trifluridine should be avoided.

Age Factors↗
PubMed1989

In vitro susceptibility of feline herpesvirus-1 to vidarabine, idoxuridine, trifluridine, acyclovir, or bromovinyldeoxyuridine.

In vitro activities of 9-[( 2-hydroxyethoxy] methyl) guanine (acyclovir), (E)-5-(2-bromovinyl)-2'deoxyuridine, 9-beta-D-arabinofuranosyladenine (vidarabine), 5-iodo-2'-deoxyuridine (idoxuridine), and 5-trifluoromethyl-2'-deoxyuridine (trifluridine) were studied against 6 strains of feline herpesvirus-1. A significant difference was not detected among viral strains in their susceptibility to these compounds (P = 0.442). The relative potency of these compounds was trifluridine much greater than idoxuridine greater than vidarabine greater than bromovinyldeoxyuridine much greater than acyclovir. Concentrations of trifluridine and idoxuridine (0.67 and 6.8 microM, respectively) required to reduce plaque numbers by 50%, compared with that of controls, were significantly lower (P less than 0.001) than were those of other compounds.

Acyclovir↗
PubMed1989

Trifluridine decreases ocular HSV-1 recovery, but not herpetic lesions after timolol iontophoresis.

To determine the effect of a topically applied antiviral agent on shedding of herpes simplex virus type 1 (HSV-1) into the tear film and corneal epithelial lesions, ten rabbits latently infected with HSV-1 were subjected to transcorneal iontophoresis of 0.01% timolol once a day for 3 consecutive days to induce viral shedding and lesions. Iontophoretic induction was performed similarly in five uninfected rabbits as controls. Half of the infected rabbits and all of the uninfected controls received topical 1.0% trifluridine five time a day for 9 days, beginning the day after the first iontophoresis. All eyes were examined daily for 10 days by slit-lamp biomicroscopy and tear film samples collected on swabs were analyzed for virus. In the infected rabbits, the eyes treated with trifluridine had significantly fewer swabs positive for HSV-1 than the untreated eyes (P less than 0.001); however, there was no significant difference in the numbers of lesions in the treated and untreated eyes. The uninfected controls had no positive swabs and developed no lesions. These results suggest that topical treatment with trifluridine may reduce recovery of HSV-1 from the tear film, but does not affect the incidence of iontophoretically induced corneal epithelial lesions.

Animals↗
PubMed1984

Human interferon alpha A or alpha D and trifluridine treatment for herpetic keratitis in rabbits.

Recombinant human interferon (IFN) alpha A and alpha D combined with 1% trifluridine ophthalmic solution gave beneficial results when applied topically at a dose of 1 x 10(6) U per eye four times a day commencing 4 hr after eyes were inoculated with herpes simplex virus (HSV-1). Acute herpetic keratitis was suppressed by trifluridine alone and the combined therapies, but the high-titered interferon preparations, alone, had little effect. Duration of HSV-1 shedding into tear film during topical treatment for acute herpetic keratitis was reduced slightly by combined therapy with either IFN alpha A or IFN alpha D with trifluridine.

Animals↗
PubMed1994

alpha-Trifluoromethyl-beta-alanyl glycine (F3MBAG): a novel mammalian metabolite of trifluridine (F3TdR).

19F NMR spectroscopy has been used to study further the metabolism of 5-trifluoromethyl-2'-deoxyuridine (trifluridine; F3TdR). The synthesis and characterization of alpha-trifluoromethyl-beta-alanyl glycine (F3MBAG), a putative new metabolite of F3TdR, are now reported. This study describes ex vivon and in vivo detection of F3MBAG and other previously reported metabolites of trifluridine, using 19F NMR spectroscopy, in male BALB/C mice bearing EMT-6 tumors. A parallel 19F NMR spectroscopic study was also performed on rats dosed with F3TdR, to observe the qualitative pattern of F3TdR metabolism in another species. Unexpectedly, 5-trifluoromethyl-5,6-dihydroxyuracil (DOHF3T), alpha-trifluoromethyl-beta-ureidopropionic acid (F3MUPA) and fluoride, which result from the metabolic degradation of F3TdR and which were detected in various biological samples from mice dosed with F3TdR, could not be identified in rat urine or in homogenized tissue extracts. The presence of these metabolites in intact tissues is uncertain since in this study 19F NMR spectroscopy of these samples always displayed a broad resonance "hump" across the range of chemical shifts that would encompass these metabolites. No clear explanation for the loss of spectroscopic resolution in this region has been rationalized. N-Carboxy-alpha-trifluoromethyl-beta-alanine (F3MBA-CO2), alpha-trifluoromethyl-beta-alanyl alanine (F3MBAA) and N-acetyl-alpha-trifluoromethyl-beta-alanine (Ac-F3MBA) were synthesized and characterized, but were not detected as metabolites in any of the biological specimens examined.

Animals↗
PubMedDate not supplied

[Trifluridine therapy in herpetic in keratitis].

The objective of the study was to analyze the efficiency of trifluridine in the treatment of herpes infection of the cornea. The study was performed on a 60 patients group suffering of different forms of herpetic keratitis. The results of the study indicate trifluridine as an efficient antiviral drug which may be successfully used in the treatment of herpetic keratitis (superficial and stromal).

Adolescent↗
PubMed1978

Inhibition of adenovirus replication in vitro by trifluridine.

At present, there is no effective chemotherapeutic agent available for the treatment of adenoviral keratoconjunctivitis. Recent evidence suggests that trifluridine (3FT) may effectively inhibit the replication of some adenovirus serotypes known to cause keratoconjunctivitis. The ability of 3FT to inhibit two reference strains of adenoviruses, type 8 and type 19, was examined using cell cultures. Two second-passage isolates of adenoviruses, identified as serotype 13, were also tested. Compared with untreated, virusinfected cell cultures, drug-treated cell cultures developed a lesser degree of cytopathic effect following infection with all three serotypes. Virus production was reduced in the drug-treated cell cultures: approximately tenfold for type 8, more than 1,000-fold for type 19, and 5,000-fold for the type 13 isolates.

Adenoviridae↗
PubMed1978

Trifluridine in resistant human herpetic keratitis.

Patients with active dendritic herpetic keratitis that was unresponsive to topical idoxuridine or vidarabine therapy were treated topically with a 1% solution of trifluridine. The dendritic ulcers healed in an average time of 6.1 days. All patients tolerated the drug well except for one patient in whom a reversible crystalline epithelial keratitis developed.

Adolescent↗
PubMed1984

Combination therapy for dendritic keratitis. High-titer alpha-interferon and trifluridine.

Previous studies showed that the combination of trifluridine with human leukocyte interferon in the treatment of dendritic keratitis is effective, and that the best results were obtained with the highest titer then available (30 X 10(6) IU/mL). The present study was undertaken to see if an even higher titer (100 X 10(6) IU/mL) would be more effective. A statistically significant greater effectiveness of the higher titer could not be verified.

Drug Therapy, Combination↗