ABSTRACT
The pharmacokinetics of acyclovir administrated orally in a dose of 200 mg every four hours, five times a day to adults with herpes progenitalis was determined. Peak plasma acyclovir levels are found 1.5 to 1.75 hours after oral administration; peak levels range from 1.4 to 4.0 microM with a mean of 2.5 microM. Acyclovir levels in saliva are well correlated with simultaneous plasma levels, saliva levels being approximately 13 percent of plasma levels. Simultaneous plasma and vaginal secretion acyclovir levels are poorly correlated; peak levels in vaginal secretions range from 0.5 to 3.6 microM.
Subject(s)
Antiviral Agents/metabolism , Guanine/analogs & derivatives , Herpes Genitalis/drug therapy , Acyclovir , Administration, Oral , Adult , Female , Guanine/metabolism , Humans , Kinetics , Male , Recurrence , Saliva/analysis , Tissue Distribution , Vagina/metabolismABSTRACT
A randomized, placebo-controlled, double-blind study was performed to evaluate the efficacy and toxicity of orally administered acyclovir in the treatment of patients with recurrent herpes simplex genitalis (HSG). A total of 107 patients from centers in Burlington, Vermont, and San Diego, California, were entered into the study within 48 hours of the onset of lesions. Patients who received acyclovir shed virus for 1.8 +/- 0.6 days (mean +/- SEM) compared with 2.8 +/- 1.2 days for those who received placebo. The duration of shedding from genital lesions of patients in the acyclovir-treated group was significantly less than from lesions of patients who received placebo (p = 0.016 by a logrank test). An analysis of the toxicity of the drug was performed in 52 of the study participants. Acyclovir was well-tolerated and no alterations were observed in measurements of bone marrow, liver, or kidney function. Orally administered acyclovir is a promising antiviral compound for the treatment of recurrent HSG.
Subject(s)
Antiviral Agents/therapeutic use , Guanine/analogs & derivatives , Herpes Genitalis/drug therapy , Acyclovir , Administration, Oral , Adult , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Clinical Trials as Topic , Double-Blind Method , Female , Guanine/administration & dosage , Guanine/adverse effects , Guanine/therapeutic use , Humans , Male , Middle Aged , Placebos , RecurrenceABSTRACT
Sixteen immunocompromised patients with herpes virus infections were treated for three to five days with continuously administered intravenous acyclovir. Patients received initial acyclovir infusions over 5 minutes in dosages ranging from 1.5 to 5.0 mg/kg followed by continuously infused acyclovir at 7.2, 14.4, 21.6, 28.8, 36.0, or 43.2 mg/kg per day. The mean serum plateau levels of acyclovir determined by radioimmunoassay ranged from 4.1 microM for the 7.2 mg/kg per day dosage to 36.6 microM for the 43.2 mg/kg per day dose. A mean of 75 percent of acyclovir administered was recovered in the urine of patients treated. Eleven of 13 patients with varicella-zoster virus (VZV) infections had no new vesicle formation after three days of acyclovir treatment and all patients ceased to have new vesicles after five days of therapy. For the nine patients from whom complete viral cultures were available, six ceased to shed virus at three days, and viral shedding ceased by five days in all patients treated with acyclovir. No clinical or laboratory adverse reactions were associated with acyclovir therapy. These data suggest that acyclovir given by continuous intravenous infusion may be useful in the treatment of herpes virus infections in immunocompromised patients.
