Antiviral efficacy of lobucavir (BMS-180194), a cyclobutyl-guanosine nucleoside analogue, in the woodchuck (Marmota monax) model of chronic hepatitis B virus (HBV) infection.
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.
Genovesi
E V
EV
Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, Connecticut, CT 06492-7660, USA. eugene.genovesi@bms.com
Lamb
L
L
Medina
I
I
Taylor
D
D
Seifer
M
M
Innaimo
S
S
Colonno
R J
RJ
Clark
J M
JM
D000818:Animals; D004279:DNA, Viral / Q000097:blood*; D004195:Disease Models, Animal; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D017919:Hepatitis B Virus, Woodchuck / Q000187:drug effects*; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D008392:Marmota; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D014766:Viremia / Q000821:virology
D004279:DNA, Viral; D018894:Reverse Transcriptase Inhibitors; D006147:Guanine; C063638:lobucavir