THE BIOAVAILABILITY AND DISPOSITION OF 1-(BETA-D-ARABINOFURANOSYL)-5-(1-PROPYNYL)URACIL (882C87), A POTENT, NEW ANTI-VARICELLA ZOSTER VIRUS AGENT

1 The bioavailability and disposition of 882C87, an anti-varicella tester virus (VZV) agent, have been investigated in healthy young and elderly volunteers. 2 The mean bioavailability of a 200 mg tablet was 21.1% in the young (range 13.3-33.0%, n = 10) and 24.6% in the elderly (range 14.4-38.4%, n = 8), which is sufficient to achieve plasma concentrations well above the IC50 for anti-VZV activity. 3 Plasma concentrations of 882C87 after 50 mg i.v. were higher in the elderly than in the young, associated with a significantly longer half-life (13.7 vs 11.8 h) and decreased renal clearance (0.11 vs 0.14 ml min(-1) kg(-1)) and total clearance (0.15 vs 0.17 ml min(-1) kg(-1)). 4 After intravenous administration, the main route of elimination of 882C87 was renal with 81.6% recovered unchanged in urine in the young and 71.2% in the elderly. The pyrimidine base, 5-propynyluracil (5-PU) was unquantifiable in plasma and only present in trace amounts in urine. 5 After oral administration to four healthy volunteers, only 17% of a dose of [C-14]- 882C87 was recovered unchanged in urine and 58% as 5-PU, with total recovery in urine accounting for 86% of the dose. There was a lag of 4-12 h before the appearance of 5-PU in plasma, peak concentrations were one-third to a half those of 882C87. The data suggest that 5-PU is formed from unabsorbed 882C87 in the gut lumen and then absorbed and excreted in urine. 6 882C87 is a potential once daily treatment for shingles.