Oral bioavailability and anti-simian varicella virus efficacy of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) in monkeys.
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.
Soike
K
K
Tulane University Regional Primate Research Center, Covington, Louisiana.
Huang
J L
JL
Tu
J I
JI
Stouffer
B
B
Mitroka
J G
JG
Swerdel
M
M
Olsen
S
S
Bonner
D P
DP
Tuomari
A V
AV
Field
A K
AK
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
D000998:Antiviral Agents; D001086:Arabinofuranosyluracil; C031368:sorivudine