Update on acyclovir: oral therapy for herpesvirus infections

The results of the major human clinical trials on oral acyclovir are reviewed, and the pharmacokinetics, adverse effects, and role of oral acyclovir in the management of herpes simplex virus (HSV) infections are discussed. Clinical studies have demonstrated the effectiveness of oral acyclovir in causing significant reductions in the duration of viral shedding, development of new lesions, and time to crusting and healing in several clinical situations. The drug appears to achieve the most dramatic results in the treatment of initial primary genital herpes infections. Oral acyclovir also has a potential role in suppressing reactivations of HSV infections in immunocompromised patients or patients experiencing greater than 10-12 recurrences of genital herpes per year. Most trials have used 200-mg capsules administered five times daily for 5-10 days for treating acute infections. Reduced doses have been successful for suppressive therapy. Acyclovir does not alter the frequency of recurrence once treatment has been discontinued. The absolute bioavailability of oral acyclovir is approximately 20%, and plasma concentrations are about one tenth of those achieved after a typical i.v. infusion. The relationship between plasma concentration and clinical response has not been established. The half-life is 3-4 hours, and the predominant route of elimination is via renal excretion and tubular secretion. Clinical studies have consistently reported minimal adverse effects with oral acyclovir. Conservative use is justified by the potential development of resistant viral strains. The extent and clinical importance of resistant viral selection remain to be determined. Oral acyclovir represents an advance in the development of a nontoxic antiviral agent suitable for both hospitalized and ambulatory patients that should be recommended for formulary inclusion.