title: In vitro and in vivo anti-herpes viral activities and biological properties of CV-araU.
abstract: We compared the in vitro and in vivo antiviral effects against herpes simplex virus type 1 (HSV-1) and other biological properties of 1-beta-D-arabinofuranosyl-5-[(E)-2-chlorovinyl]uracil (CV-araU) and 1-beta-D-arabinofuranosyl-5-[(E)-2-bromovinyl]uracil (BV-araU, sorivudine). Both CV-araU and BV-araU exhibited antiviral activities against HSV-1 in the cell culture derived from mouse, though the activities were lower than those seen in human cells. For intraperitoneal and intracerebral infections in mice with HSV-1 strain WT-51, both compounds, administered twice daily, were effective in increase in the survival rate at doses of 15 mg/kg and 30 mg/kg, respectively. In pharmacokinetic analysis, both drugs were absorbed well in the rat gastrointestinal tract following oral administration. There was no difference between the metabolism of orally administered CV-araU and BV-araU in rats. High levels of the corresponding base were found in plasma after oral administration of CV-araU and BV-araU, but much lower base levels were seen after intravenous doses. Both drugs were resistant to degradation by rat liver enzymes.
authors.affiliation: Biology Laboratory, Yamasa Corporation, Choshi, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Ashida
authors.forename: S
authors.initials: S
authors.lastname: Sakata
authors.forename: F
authors.initials: F
authors.lastname: Kano
authors.forename: M
authors.initials: M
authors.lastname: Nishitani
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: H
authors.initials: H
authors.lastname: Machida
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D001966:Bromine / Q000737:chemistry; D002460:Cell Line; D002713:Chlorine / Q000737:chemistry; D018792:Encephalitis, Viral / Q000188:drug therapy; D006561:Herpes Simplex / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D006801:Humans; D008297:Male; D051379:Mice; D051381:Rats
chemical_list: D000998:Antiviral Agents; D001086:Arabinofuranosyluracil; D002713:Chlorine; C031369:1-beta-arabinofuranosyl-5-(2-chlorovinyl)uracil; C031368:sorivudine; D001966:Bromine