title: 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.
authors.affiliation: Tulane University Regional Primate Research Center, Covington, Louisiana.
authors.forename: K
authors.initials: K
authors.lastname: Soike
authors.forename: J L
authors.initials: JL
authors.lastname: Huang
authors.forename: J I
authors.initials: JI
authors.lastname: Tu
authors.forename: B
authors.initials: B
authors.lastname: Stouffer
authors.forename: J G
authors.initials: JG
authors.lastname: Mitroka
authors.forename: M
authors.initials: M
authors.lastname: Swerdel
authors.forename: S
authors.initials: S
authors.lastname: Olsen
authors.forename: D P
authors.initials: DP
authors.lastname: Bonner
authors.forename: A V
authors.initials: AV
authors.lastname: Tuomari
authors.forename: A K
authors.initials: AK
authors.lastname: Field
mesh_terms: D000284:Administration, Oral; D000327:Adsorption; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001086:Arabinofuranosyluracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D001682:Biological Availability; D002478:Cells, Cultured; D002644:Chickenpox / Q000188:drug therapy*; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D005260:Female; D014645:Herpesvirus 3, Human / Q000187:drug effects; D008297:Male
chemical_list: D000998:Antiviral Agents; D001086:Arabinofuranosyluracil; C031368:sorivudine