VALACICLOVIR - A REVIEW OF ITS ANTIVIRAL ACTIVITY, PHARMACOKINETIC PROPERTIES AND THERAPEUTIC EFFICACY IN HERPESVIRUS INFECTIONS

Valaciclovir, the L-valyl ester of aciclovir (acyclovir), is an oral p rodrug that undergoes rapid and extensive first-pass metabolism to yie ld aciclovir and the essential amino acid L-valine. Aciclovir, the act ive antiviral component of valaciclovir, shows good in vitro activity against the herpesviruses herpes simplex virus (HSV)-1, HSV-2 and vari cella zoster virus. The bioavailability of aciclovir from oral valacic lovir is considerably greater than that achieved after oral aciclovir administration. Thus, valaciclovir delivers therapeutic aciclovir conc entrations when administered in a less frequent oral dosage regimen th an is required for aciclovir. Valaciclovir is an effective treatment f or herpes zoster in immunocompetent adults. In a large comparative stu dy that included patients greater than or equal to 50 years of age, va laciclovir (1000mg 3 times daily for 7 or 14 days) and oral aciclovir (800mg 5 times daily) were equally effective in achieving resolution o f cutaneous zoster lesions. Importantly, valaciclovir was significantl y more effective than aciclovir in reducing the duration of zoster-ass ociated pain. Preliminary results of several studies indicate that val aciclovir (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 gen ital herpes, valaciclovir reduced the duration of viral shedding, hast ened lesion healing and decreased lesion-associated pain. Valaciclovir was also effective in suppressing recurrent episodes of genital herpe s and significantly prolonged the time to a recurrent episode of infec tion 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 an advance in an tiherpes drug therapy and is a useful treatment option for patients wi th herpes zoster or genital herpes. It is at least as effective as aci clovir and is administered in a more convenient oral dosage regimen. T hus, valaciclovir may ultimately succeed aciclovir as a first-line tre atment for genital herpes or herpes zoster.