There was a significant reduction in acute herpes zoster pain with famciclovir on day 7 and at weeks in both of these patient groups, while with valacyclovir, there was not significant reduction in pain on day 7.
Of patients aged 50 years or older, there was a significantly earlier reduction in pain with famciclovir than with valacyclovir. In addition, a significant reduction in the number of patients with pain was observed as early as days with famciclovir treatment as compared with valacyclovir treatment. We conclude that famciclovir was superior to valacyclovir in the relief of acute pain of herpes zoster.
Antiviral drugs are designed to inhibit the multiplication of viruses in the body. Unlike antibiotics, which eliminate the bacteria that cause infections, antiviral drugs simply control viral proliferation, rather than completely eliminating the target virus from the body.
None of the antiviral drugs on the market today can cure herpes. However, consistent use of an antiviral drug can make living with herpes much easier by speeding up healing after an outbreak and reducing your risk of transmitting the virus to other people.
Herpes drugs are taken for several reasons. Antiviral drugs are also used as part of suppressive therapy for herpes to reduce the severity and frequency of outbreaks.
Even people with asymptomatic herpes can benefit from using antiviral drugs to lower their risk of spreading the virus to other people through sexual or oral contact. Valacyclovir is one of the most widely used drugs for treating herpes. Most people know of this drug as Valtrex , a brand name used to market the medication by GlaxoSmithKline. Valacyclovir is a prodrug , meaning it converts into another drug inside the body. Acyclovir then blocks the herpes virus from reproducing, helping to control the symptoms of a herpes outbreak.
Like other herpes medications, valacyclovir is highly effective. Studies show that it reduces the amount of time required for healing during a herpes outbreak, as well as reducing your risk of transmitting the herpes virus to other people. Valacyclovir starts working almost as soon as you start taking it. One of the top reasons to use valacyclovir vs. Acyclovir is almost completely broken down by the liver when taken orally, whereas valacyclovir has an oral bioavailability level of approximately 50 percent compared to approximately 12 percent for oral acyclovir.
This means that more of the drug makes it into your body, helping to control a herpes outbreak and reduce your risk of transmitting the virus. Both drugs significantly reduced mortality and titers of virus shed from the eyes of mice infected with an otherwise lethal dose of HSV type 1 HSV Similar titers of HSV-1 were found in the eyes, ganglia, and brains of treated animals. Although valacyclovir reduced the latent viral DNA load better in these studies than did famciclovir, rates of reactivation by explantation and UV exposure were the same.
Thus, in this study, famciclovir and valacyclovir were equally effective in limiting the virulence and spread of HSV-1, despite their biochemical and pharmacologic differences. Herpes simplex virus HSV types 1 and 2 are important human pathogens that cause orofacial and genital lesions [ 1 ]. During the initial infection, HSV infects neurons, where it remains in a latent state until reactivated by stimuli such as heat and UV light [ 2 , 3 ]. In vivo reactivation of HSV depends on multiple factors, such as the anatomic site of infection [ 4 ], the host's immune status [ 5—7 ], and the quantity of latent viral DNA [ 8 ].
Currently, there is no vaccine or cure for HSV infections; however, treatments are available that diminish the severity of the disease.
Valacyclovir and famciclovir, the oral forms of acyclovir and penciclovir, respectively, are guanine analogues that inhibit HSV replication at the level of DNA synthesis [ 9—16 ]. Following their absorption, valacyclovir and famciclovir are rapidly and efficiently metabolized by host enzymes to acyclovir and penciclovir, respectively.
Both acyclovir and penciclovir enter infected and uninfected cells but require viral thymidine kinase for activity [ 9 , 14 , 15 ]. Previous reports showed that penciclovir has a higher affinity than acyclovir for the viral thymidine kinase, a faster rate of phosphorylation, and a longer intracellular half-life [ 10 , 11 ]; however, penciclovir has a lower affinity than acyclovir for the HSV DNA polymerase. The end result is that the penciclovir prodrug, famciclovir, which is effective in humans at doses similar to those for acyclovir, can be given less often.
The higher acyclovir blood levels effected by valacyclovir achieve the same end result of reduced dosage frequency. Given these modest differences between valacyclovir and famciclovir, it is noteworthy that a series of animal studies suggested that famciclovir is better than valacyclovir in terminating ganglionic HSV infection and thereby limits subsequent reactivation [ 17—20 ].
We investigated the effects of oral famciclovir and valacyclovir on HSV-1 infection, establishment of latency, and reactivation in the mouse eye model. Our conclusions differ from those summarized above [ 17—20 ]. Hereafter we refer to this medium as EMEM medium.
Mice were anesthetized with a 0. Drug-treated animals received either famciclovir or valacyclovir both from Midwest Medical Supply, St. Water bottles were changed daily to ensure fresh drug preparations. Mice were infected by bilateral corneal scarification and were observed daily for mortality up to pi day Concurrent with survival monitoring, the quantity of virus shed from the inoculation site was determined. On the indicated days, both eyes were swabbed with a moistened Dacron polyester-tipped applicator Baxter Healthcare, Deerfield, IL.
Afterward, cells were overlaid with medium containing 0. The dishes were then stained and plaques were counted. Plaques were identified and counted as indicated earlier. Animals that survived the HSV-1 infection were allowed to develop latent infections by housing them for at least 30 days after infection. Whole TG from groups of 10 latently infected mice were removed, and each pair of TG was placed onto separate Vero cell monolayers.
The explants were checked daily for cytopathic effects CPEs and carefully transferred onto fresh monolayers weekly, if necessary.
The eyes of latently infected mice were exposed to UV radiation to reactivate HSV-1 in vivo by use of a modified procedure of Laycock et al [3]. One side of the head was exposed for 1 min. Mice were then turned to expose their contralateral eye. Monolayers were checked daily for CPEs. TG pairs from latently infected mice were dissected by use of individual sterile instruments for each animal. A positive control plasmid, pSG25 [ 21 , 22 ] obtained from M.
Comparisons between the Kaplan-Meier survival estimates were done by log-rank test. Nonparametric methods were used to analyze other data. Geometric means and one-way analysis of variance with log-transformed numbers were used to analyze results from ocular swabs, acute-phase tissue virus titers, and quantitative PCR.
Means, medians, and distributions were compared by the Wilcoxon two-sample test. The proportions of samples reactivating by explant and by UV stress were compared by two-tailed Fisher's exact test. To define the effects of famciclovir and valacyclovir on virus-induced mortality, groups of 25 animals were infected by bilateral corneal scarification followed by inoculation with 10 6 pfu of HSV-1 McKrae.
Mortality was scored daily for the first 15 pi days. None of the untreated animals survived beyond pi day 5, whereas all of the mock-infected animals survived. Thus, both drugs allowed similar percentages of mice to survive an otherwise lethal inoculum of HSV Survival after herpes simplex virus type 1 HSV-1 inoculation.
Survival was monitored for first 15 pi days. To monitor the titers of HSV-1 shed at the site of inoculation, eye swabs were taken on pi days 1, 2, 5, 7, 12, and On pi day 1, all infected animals shed 5 logs of virus; the amount of shedding decreased over time figure 2.
There were no survivors in the untreated group of mice after pi day 5. However, there was no significant difference in the titers of virus shed from the famciclovir- and valacyclovir-treated groups P by pi day 1,. Ocular shedding after herpes simplex virus type 1 HSV-1 infection. On indicated days, corneal swabs were taken for virus isolation and titration. Log values of 0 reflect un-detectable virus levels. Subsequent to the initial eye infection, the virus spread to the TG and then to the brain.
To study HSV-1 pathogenesis in this mouse model, we quantified the amount of virus found in the eyes, TG, and brain on pi days 2, 4, 7, 9, and These tissues were removed from groups of 3 euthanized mice per treatment arm and at each time point.
The experiment was done twice, and the results shown are the combined data for 6 mice per data point. As expected, there were higher tissue titers in untreated animals than in those treated figure 3.
Except for 1 data point, HSV titers in the eyes, TG, and brains of famciclovir-treated mice were similar to those given valacyclovir figure 3.
P values by pi days 2, 4, 7, 9, and 11, respectively, were as follows: eyes,. A progression of infection was evident as virus titers in the TG peaked on pi day 4 for all 3 groups, whereas titers in the brain peaked on pi day 7. Untreated controls did not survive after pi day 7.
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