Pharmacokinetics: The pharmacokinetics of acyclovir after oral administration have been evaluated in healthy volunteers and in immunocompromised patients with herpes simplex or varicella-zoster virus infection. Acyclovir pharmacokinetic parameters are summarized in Error! Hyperlink reference not valid.. 

In one multiple-dose, crossover study in healthy subjects (n = 23), it was shown that increases in plasma Acyclovir concentrations were less than dose proportional with increasing dose, as shown in Error! Hyperlink reference not valid.. The decrease in bioavailability is a function of the dose and not the dosage form. 

There was no effect of food on the absorption of acyclovir (n = 6); therefore, acyclovir capsules may be administered with or without food.

The only known urinary metabolite is 9-[(carboxymethoxy)methyl]guanine.

Special Populations: Adults with Impaired Renal Function: The half-life and total body clearance of acyclovir are dependent on renal function. A dosage adjustment is recommended for patients with reduced renal function (see DOSAGE AND ADMINISTRATION). 

Geriatrics: Acyclovir plasma concentrations are higher in geriatric patients compared with younger adults, in part due to age-related changes in renal function. Dosage reduction may be required in geriatric patients with underlying renal impairment (see Error! Hyperlink reference not valid.). 

Pediatrics: In general, the pharmacokinetics of acyclovir in pediatric patients is similar to that of adults. Mean half-life after oral doses of 300 mg/m 2 and 600 mg/m 2 in pediatric patients aged 7 months to 7 years was 2.6 hours (range 1.59 to 3.74 hours). 

Drug Interactions: Coadministration of probenecid with intravenous acyclovir has been shown to increase the mean acyclovir half-life and the area under the concentration-time curve. Urinary excretion and renal clearance were correspondingly reduced. 

Clinical Trials: Initial Genital Herpes: Double-blind, placebo-controlled studies have demonstrated that orally administered acyclovir significantly reduced the duration of acute infection and duration of lesion healing. The duration of pain and new lesion formation was decreased in some patient groups. 

Recurrent Genital Herpes: Double-blind, placebo-controlled studies in patients with frequent recurrences (6 or more episodes per year) have shown that orally administered acyclovir given daily for 4 months to 10 years prevented or reduced the frequency and/or severity of recurrences in greater than 95% of patients. 

In a study of patients who received acyclovir 400 mg twice daily for 3 years, 45%, 52%, and 63% of patients remained free of recurrences in the first, second, and third years, respectively. Serial analyses of the 3-month recurrence rates for the patients showed that 71% to 87% were recurrence free in each quarter. 

Herpes Zoster Infections: In a double-blind, placebo-controlled study of immunocompetent patients with localized cutaneous zoster infection, acyclovir (800 mg 5 times daily for 10 days) shortened the times to lesion scabbing, healing, and complete cessation of pain, and reduced the duration of viral shedding and the duration of new lesion formation. 

In a similar double-blind, placebo-controlled study, acyclovir (800 mg 5 times daily for 7 days) shortened the times to complete lesion scabbing, healing, and cessation of pain; reduced the duration of new lesion formation; and reduced the prevalence of localized zoster-associated neurologic symptoms (paresthesia, dysesthesia, or hyperesthesia). 

Treatment was begun within 72 hours of rash onset and was most effective if started within the first 48 hours. 

Adults greater than 50 years of age showed greater benefit. 

Chickenpox: Three randomized, double-blind, placebo-controlled trials were conducted in 993 pediatric patients aged 2 to 18 years with chickenpox. All patients were treated within 24 hours after the onset of rash. In 2 trials, acyclovir was administered at 20 mg/kg 4 times daily (up to 3,200 mg per day) for 5 days. In the third trial, doses of 10, 15, or 20 mg/kg were administered 4 times daily for 5 to 7 days. 

Treatment with acyclovir shortened the time to 50% healing; reduced the maximum number of lesions; reduced the median number of vesicles; decreased the median number of residual lesions on day 28; and decreased the proportion of patients with fever, anorexia, and lethargy by day 2. Treatment with acyclovir did not affect varicella-zoster virus-specific humoral or cellular immune responses at 1 month or 1 year following treatment.