882C87 [1-(beta-D-arabinofuranosyl)-5-propynyluracil] is a nucleoside analogue with potent and specific antiviral activity against varicella-zoster virus (VZV). The IC50 of 882C87 against VZV ranges from 0.6 to 3.8 microM. Potentially therapeutic plasma concentrations are readily achieved in humans; the pharmacokinetics have been previously evaluated in healthy young and elderly (> 65 years) volunteers following single oral doses of 50-400 mg. Thirty immunocompetent patients with localised herpes zoster were treated with 882C87. Groups of patients received 50 mg, 100 mg, or 200 mg tablets of 882C87 every 12 hours for 7 or 7.5 days (14 or 15 doses). Six patients in each group were over 60 years of age. Blood samples for determination of 882C87 concentrations were taken at entry, steady state, and during the elimination phase following the last dose. After the final doses of the 50 mg 100 mg, and 200 mg dosage regimens, the Cmax of 882C87 in patients over 60 years old was 7.7 +/- 3.1 microM, 12.6 +/- 3.5 microM, and 24.8 +/- 14.0 microM, respectively, and the AUCs 0-12 were 78.4 +/- 31.8 microM.hr, 137.5 +/- 22.8 microM.hr, and 272.5 +/- 170.5 microM.hr, respectively. Preliminary estimates of the elimination half-life ranged from 15.1 to 20.0 hr. These preliminary pharmacokinetic data confirmed good dose proportionality for AUC and Cmax with values between those predicted from single dose data in the young and those in elderly volunteers. The plasma concentration profiles at these doses were in excess of IC50 values and support the use of once- or twice-daily regimens in future studies of 882C87 in herpes zoster.