Effects of Anti Herpetic Drugs on Mice with Herpetic Epithelial Keratitis After Reactivation of Herpes Simplex Virus Type 1

Abstract

To compare the efficacies of valacyclovir (VCV) and acyclovir (ACV) on murine herpetic epithelial keratitis, mice inoculated with herpes simplex virus type 1(HSV-1) strain McKrae were divided into 6 treatment groups: oral VCV 50 mg/kg and 100 mg/kg, oral ACV 50 mg/kg, ACV eye ointment (EO), ACV eye drops (ED), and placebo. Keratitis scores showed that oral VCV 50 mg/kg, oral ACV, and ACV ED had equivalent efficacies, while oral VCV 100 mg/kg was as efficacious as ACV EO during acute infection. Each treatment group was further divided into the stimulated group with HSV-1 reactivation by immunosuppressant drugs and hyperthermia, and the non-stimulated group without reactivation. We assessed the virus titers in tissues by plaque assay and HSV DNA copy number in the trigeminal ganglia (TG) by real time polymerase chain reaction (PCR). Results showed that the virus titers in the tissues were lowered after reactivation, and the oral VCV group with reactivation had significantly reduced DNA copy number in the TG than the same treatment group without reactivation. In conclusion, oral VCV is as efficacious as ACV EO and significantly suppresses HSV-1 reactivation.

Evaluation of orally administered famciclovir in cats experimentally infected with feline herpesvirus type-1

“…However, orally administered valacyclovir and famciclovir have been used to treat herpetic epithelial keratitis caused by HSV-1 in humans, experimentally induced HSV-1 infections in rabbits and mice, and corneal disease in cats. [34][35][36][37][38] Future studies to assess the concentration of penciclovir in tears, corneal tissue, and conjunctival tissue are necessary.…”

Pharmacokinetics of famciclovir and penciclovir in tears following oral administration of famciclovir to cats: a pilot study

“…This observation may reflect the inability of a systemically administered medication to achieve therapeutic concentrations at the corneal surface or within the avascular corneal stroma. Although orally administered valacyclovir or famciclovir has been used to treat epithelial keratitis caused by HSV‐1 in humans and experimentally‐induced HSV‐1 infections in rabbits and mice, 14–16 to the authors’ knowledge the concentration of penciclovir required at the corneal surface for effective control of herpetic disease has not been reported in any species, including humans.…”

Aciclovir‐resistant herpes keratitis

“…With the advent of new therapies in the last 15 years, many clinicians manage refractory disease with oral aciclovir or valaciclovir 4 . Prophylaxis against recurrent disease has been proven with oral aciclovir 400 mg twice a day, 5 but oral valaciclovir 500 mg daily is now commonly used instead 6,7 …”