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Oral bioavailability and anti-simian varicella virus efficacy of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) in monkeys.

Abstract
BV-araU (1-beta-D-arabinofuranosyl-E-5-[2-bromovinyl]uracil) has potent antiviral activity against varicella zoster virus in cell culture and is undergoing clinical evaluation. In the present study, pharmacokinetic parameters and the efficacy of BV-araU against infection with simian varicella virus (SVV) were evaluated in African green monkeys. Pharmacokinetic parameters were determined by analysis of the BV-araU content of sera obtained after oral and intravenous administration to normal monkeys. Peak serum concentrations showed dose proportionality, with the 0.1 mg/kg dose resulting in a peak serum concentration of 0.05 micrograms/ml, the approximately ED50 value for the SVV inoculum in cell culture. BV-araU administered orally twice daily at 0.1 mg/kg for 10 days starting 48 h after intratracheal SVV infection prevented vesicular rash development and suppressed viremia. Effective therapy could be initiated 96 h after infection. Taken together, these results indicate that BV-araU is effective oral therapy at doses that achieve peak serum levels equivalent to the ED50 for SVV in cell culture.
AuthorsK Soike, J L Huang, J I Tu, B Stouffer, J G Mitroka, M Swerdel, S Olsen, D P Bonner, A V Tuomari, A K Field
JournalThe Journal of infectious diseases (J Infect Dis) Vol. 165 Issue 4 Pg. 732-6 (Apr 1992) ISSN: 0022-1899 [Print] UNITED STATES
PMID1313071 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antiviral Agents
  • Arabinofuranosyluracil
  • sorivudine
Topics
  • Administration, Oral
  • Adsorption
  • Animals
  • Antiviral Agents (administration & dosage, pharmacokinetics, pharmacology, therapeutic use)
  • Arabinofuranosyluracil (administration & dosage, analogs & derivatives, pharmacokinetics, pharmacology, therapeutic use)
  • Biological Availability
  • Cells, Cultured
  • Cercopithecus aethiops
  • Chickenpox (drug therapy)
  • Dose-Response Relationship, Drug
  • Female
  • Herpesvirus 3, Human (drug effects)
  • Male

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