Affiliation:
1. Division of Gastroenterology, Stanford University School of Medicine, Stanford, California 94305-5187
2. Hepadnavirus Testing, Inc., Mountain View, California 94043-1757
3. Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492
Abstract
ABSTRACT
The ability of entecavir (ETV) to inhibit
Duck hepatitis B virus
(DHBV) infection in duck hepatocytes and ducklings was examined using lamivudine (3TC) as a comparator drug. ETV exhibited antiviral activity (50% effective concentration [EC
50
], 0.13 nM) in DHBV-infected duck hepatocytes that was >1,000-fold more potent than that of 3TC (EC
50
, 138 nM). A 21-day treatment of ducklings with 1 mg of ETV per kg of body weight per day by oral gavage resulted in a mean reduction of log
10
3.1 in serum DHBV DNA levels. Daily treatment with 0.1 mg of ETV/kg was nearly as effective, achieving an average viral DNA level decrease of log
10
2.1. Reducing the daily dose of ETV to only 0.01 mg/kg resulted in an average viral DNA level decrease of log
10
0.97. Daily treatment with 25 mg of 3TC/kg resulted in an average viral DNA level decrease of log
10
0.66, compared to the log
10
0.20 drop seen for ducklings given the vehicle alone. ETV was also more effective in decreasing the DHBV DNA levels in duck livers after 21 days of treatment, causing average drops of log
10
1.41, log
10
0.76, and log
10
0.26 for dose levels of 1.0, 0.1, and 0.01 mg/kg, respectively, compared to a decrease of log
10
0.06 for 3TC at a dose level of 25 mg/kg. Levels of viral covalently closed circular DNA in the treatment group receiving 1 mg of ETV/kg were reduced compared to those in the vehicle-treated group. ETV and 3TC were both well tolerated in all treated animals. These results show that ETV is a highly potent and effective antiviral in the DHBV duck model.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
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