Multiple dose netivudine, a potent anti-varicella zoster virus agent, in healthy elderly volunteers and patients with shingles

The Journal of Antimicrobial Chemotherapy
R PeckR J Crooks

Abstract

Netivudine is a nucleoside analogue with potent anti-varicella zoster virus activity. We now report two open studies of the pharmacokinetics and tolerability of netivudine in doses of 50, 100 and 200 mg twice daily. In one study, healthy volunteers received an initial, single dose followed, a week later, by repeat dosing for 9 1/2 days; in the other, patients with shingles were treated for 8 days and data were also recorded for rash resolution and pain duration and intensity. Netivudine was well tolerated in both studies. Plasma concentrations were similar in patients and healthy volunteers and increased in proportion to dose. Steady state concentrations were 15-25% lower than expected from single dose data, probably because of slightly decreased netivudine absorption after food. Elimination half-life was l4-20 h. Plasma concentrations 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 elevated for up to 72 h after the last netivudine dose, suggesting continued but slow release from unabsorbed netivudine in the gut lumen. New lesion formation ceased and vesicles crusted most quickly...Continue Reading

Citations

Aug 31, 2001·Antiviral Chemistry & Chemotherapy·C McGuiganJ Balzarini
May 17, 2008·Special Care in Dentistry : Official Publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry·M O Cox
Sep 15, 2020·European Journal of Medicinal Chemistry·Deepthi RameshTharanikkarasu Kannan

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