MULTIPLE-DOSE NETIVUDINE, A POTENT ANTI-VARICELLA ZOSTER VIRUS AGENT,IN HEALTHY ELDERLY VOLUNTEERS AND PATIENTS WITH SHINGLES

Netivudine is a nucleoside analogue with potent anti-varicella tester virus activity. We now report two open studies of the pharmacokinetics and tolerability of netivudine in doses of 50, 100 and 200 mg twice d aily. In one study, healthy volunteers received an initial, single dos e followed, a week later, by repeat dosing for 91/2 days; in the other , patients with shingles were treated for 8 days and data were also re corded for rash resolution and pain duration and intensity. Netivudine was well tolerated in both studies. Plasma concentrations were simila r in patients and healthy volunteers and increased in proportion to do se. Steady state concentrations were 15-25% lower than expected from s ingle dose data, probably because of slightly decreased netivudine abs orption after food. Elimination half-life was 14-20 h. Plasma concentr ations of 5-propynyluracil (5-PU), the main metabolite of netivudine, did not increase in proportion to the netivudine dose and tended to be higher in patients than volunteers. 5-PU concentrations remained elev ated for up to 72 h after the last netivudine dose, suggesting continu ed but slow release from unabsorbed netivudine in the gut lumen. New l esion formation ceased and vesicles crusted most quickly in the 200 mg group; tester-associated pain intensity, was reduced in a dose-relate d manner.