Medline ® Abstracts for References 2,3
of 'Valacyclovir: An overview'
New antiherpesvirus agents. Their targets and therapeutic potential.
Alrabiah FA, Sacks SL
Of the large number of agents under development for the treatment of herpes virus infections [herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV)], only ten have apparently reached clinical development. Aciclovir was approved for the treatment of HSV infections over 10 years ago, and it remains an important and reliable antiviral agent. Recent approvals in some countries of valaciclovir for VZV infection and famciclovir for both HSV and VZV infections demonstrate the rapidity of change in this field. Intravenous ganciclovir and foscarnet are approved for the treatment of CMV infection in the immunocompromised patient. Five of the antiherpetic drugs under current clinical development are nucleoside analogues or their prodrugs; another is a phosphorylated nucleoside (nucleotide). Four of the nucleoside agents-penciclovir, famciclovir, valaciclovir and lobucavir-are being developed for the management of HSV and VZV infections. Valaciclovir is also being developed for the prevention of CMV infections and famciclovir and lobucavir for the treatment of hepatitis B virus infection. Oral ganciclovir, lobucavir, ISIS 2922 and cidofovir are being developed for the suppression of CMV infections in immunocompromised patients. Sorivudine has been studied in VZV infections. n-Docosanol is under development for HSV infections, and cidofovir is being developed for both HSV and CMV infections, as well as for treatment of other viral diseases. Traditionally, the adverse effects associated with anti-CMV compounds have been more difficult to manage and are acceptable clinically only because of the severity of the underlying infection and lack of safer therapeutic alternatives. In general, toxicity issues continue to be problematic in the anti-CMV arena, although newer agents have improved the situation to some extent. In contrast, the safety of anti-HSV compounds has traditionally been excellent, establishing a safety standard that must be met by newer agents entering the field.
Department of Medicine, University of British Columbia, Vancouver, Canada.
Valaciclovir. A review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in herpesvirus infections.
Perry CM, Faulds D
Valaciclovir, the L-valyl ester of aciclovir (acyclovir), is an oral prodrug that undergoes rapid and extensive first-pass metabolism to yield aciclovir and the essential amino acid L-valine. Aciclovir, the active antiviral component of valaciclovir, shows good in vitro activity against the herpesviruses herpes simplex virus (HSV)-1, HSV-2 and varicella zoster virus. The bioavailability of aciclovir from oral valaciclovir is considerably greater than that achieved after oral aciclovir administration. Thus, valaciclovir delivers therapeutic aciclovir concentrations when administered in a less frequent oral dosage regimen than is required for aciclovir. Valaciclovir is an effective treatment for herpes zoster in immunocompetent adults. In a large comparative study that included patients>or = 50 years of age, valaciclovir (1000mg 3 times daily for 7 or 14 days) and oral aciclovir (800mg 5 times daily) were equally effective in achieving resolution of cutaneous zoster lesions. Importantly, valaciclovir was significantly more effective than aciclovir in reducing the duration of zoster-associated pain. Preliminary results of several studies indicate that valaciclovir (500 to 1000mg twice daily for 5 to 10 days) is as effective as aciclovir (200mg 5 times a day for 5 to 10 days) in the treatment of genital herpes. In patients with first or recurrent episodes of genital herpes, valaciclovir reduced the duration of viral shedding, hastened lesion healing and decreased lesion-associated pain. Valaciclovir was also effective in suppressing recurrent episodes of genital herpes and significantly prolonged the time to a recurrent episode of infection compared with placebo. Valaciclovir is a well tolerated drug; in herpes zoster and HSV studies its tolerability profile was similar to that of aciclovir or placebo. Valaciclovir represents and advance in antiherpes drug therapy and is a useful treatment option for patients with herpes zoster or genital herpes. It is at least as effective as aciclovir and is administered in a more convenient oral dosage regimen. Thus, valaciclovir may ultimately succeed aciclovir as a first-line treatment for genital herpes or herpes zoster.
Adis International Limited, Auckland, New Zealand.