Abstract
Although aciclovir has been the most extensively used nucleoside analogue for the treatment of genital herpes, its poor bioavailability, frequent dosing (five times daily), and the short intracellular half-life of the active triphosphate (≤1–2 h) has led to the development of a new generation of agents. The prodrug valaciclovir (active agent aciclovir), and famciclovir (active agent penciclovir) have improved pharmacokinetics compared with aciclovir. Compared with oral aciclovir, valaciclovir yields aciclovir with three-fivefold higher serum levels and the oral prodrug famciclovir yields even higher serum levels of penciclovir. The active agent, penciclovir triphosphate, has a prolonged intracellular half-life in vitro [10 h for cells infected with herpes simplex virus type 1 (HSV-1) and 20 h for HSV-2-infected cells]. Evidence also suggests that famciclovir may have an effect on the establishment of latency in primary infection, thus reducing the risk of subsequent recurrent disease. Ongoing clinical trials are underway exploring this possibility. For patients with frequent recurrences of genital herpes, or patients psychologically disabled by the condition, twice-daily antiviral therapy offers the most effective reduction in the frequency of clinical recurrence. Twice-daily therapy also has the advantage that patients are at less risk of asymptomatic breakthrough and the potential risk of transmission if they forget to take one dose.