Journal of Antimicrobial Chemotherapy (1996) 37, 583-597
© 1996 The British Society for Antimicrobial Chemotherapy
research-article |
Multiple dose netivudine, a potent anti-varicella zoster virus agent, in healthy elderly volunteers and patients with shingles
aWellcome Research Laboratories Beckenham, Kent, BR3 3BS, UK. bKeele University School of Postgraduate Medicine, North Staffordshire Hospital Stok-on-Trent, ST4 7QB, UK. cBirmingham Heartlands Hospital Birmingham, B9 5ST, UK. dRoyal Hallamshire Hospital Sheffield, S10 2JT, UK. eCoppetts Wood Hospital London, N10 1JN, UK. fNorth Manchester General Hospital Manchester, M8 5RB, UK.
Received 13 June 1995; returned 6 September 1995; accepted 19 October 1995
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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
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 14–20 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 in the 200 mg group; zoster-associated pain intensity, was reduced in a dose-related manner.