Antiviral efficacy of lobucavir (BMS-180194), a cyclobutyl-guanosine nucleoside analogue, in the woodchuck (Marmota monax) model of chronic hepatitis B virus (HBV) infection.

Abstract

Lobucavir (BMS-180194), a cyclobutyl-guanosine nucleoside analogue, effectively reduced WHV-viremia in chronically infected carrier woodchucks (Marmota monax) by daily per os treatment. WHV-viremia in the animals was measured by the serum content of hybridizable WHV-genomic DNA. Lobucavir, given at daily doses of 10 and 20 mg/kg body weight, reduced WHV-viremia by a 10- to 200-fold range during therapy. Lobucavir, given at 5 mg/kg, suppressed WHV-viremia by a 10- to 30-fold range, whereas a 0.5 mg/kg dose had no significant effect. WHV-viremia was also measured by hepadnaviral endogenous polymerase activity (EPA) in sera of animals treated for 6 weeks at 5 and 0.5 mg/kg. Changes in EPA in sera of lobucavir treated animals were comparable to changes in WHV DNA levels. Viremia in treated carriers recrudesced to pretreatment levels by 2 weeks of therapy cessation. These results indicated that the minimally effective antiviral daily per os dose of lobucavir in WHV-carrier woodchucks was approximately 5 mg/kg.

• Authors: E V Genovesi, L Lamb, I Medina, D Taylor, M Seifer, S Innaimo, R J Colonno, J M Clark
• Journal: Antiviral research (Antiviral Res) Vol. 48 Issue 3 Pg. 197-203 (Dec 2000) ISSN: 0166-3542 [Print] Netherlands
• PMID: 11164506 (Publication Type: Journal Article)

Chemical References

• DNA, Viral
• Reverse Transcriptase Inhibitors
• Guanine
• lobucavir

Topics

• Animals
• DNA, Viral (blood)
• Disease Models, Animal
• Guanine (analogs & derivatives, pharmacology, therapeutic use)
• Hepatitis B Virus, Woodchuck (drug effects)
• Hepatitis B, Chronic (drug therapy, virology)
• Humans
• Marmota
• Reverse Transcriptase Inhibitors (pharmacology, therapeutic use)
• Viremia (virology)