Evaluation of the Potent Anti-Hepatitis B Virus Agent (-) cis-5-Fluoro-1-[2-(Hydroxymethyl)-1,3-Oxathiolan-5-yl]Cytosine in a Novel In Vivo Model

A murine model was developed to investigate the in vivo activity of anti-hepatitis B virus (HBV) agents. Mice with subcutaneous tumors of HBV-producing 2.2.15 cells showed reductions in levels ofHBV in serum and in intracellular levels of HBV when the mice were orally dosed with (-) cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine (FEC). No effects on tumor size or alpha-fetoprotein levels were observed. FIC can selectively inhibit HBV replication at nontoxic doses. The majority of in vivo studies of potential anti-hepatitis B virus (HBV) agents have been performed with Pekin ducks infected with duck HBV (7, 12-14, 21, 24), although systems using Beechey ground squirrels and woodchucks infected with ground squirrel and woodchuck hepatitis viruses, respectively, have been developed (16, 23). These systems vary with respect to the involvement of the immune component in the disease. All of these models involve relatively large animals which require substantial quantities of compound for evaluation and are difficult to manage in most laboratories. Also, testing o