Harmenberg J, Ageland H, Borg N, Bottiger D, Johansson NG, Lofgren B, Oberg B, Pelcman M, Schroder I, Stahle L, Vrang L, Zhang H, Zhou XX; International Conference on Antiviral Research.
Antiviral Res. 1998 Mar; 37: A65 (abstract no. 90).
Medivir AB, Huddinge, Sweden.
FLG (2',3'-dideoxy-3'fluoroguanosine) is a nucleoside analogue, which inhibits duck hepatitis B virus in primary duck hepatocytes with an IC50 of 0.05 micromolar. Comparative in vitro experiments have shown FLG to be 10-fold more active than 3TC and penciclovir. Inhibition of cell growth was observed at 200 micromolar. FLG was also inhibitory to HIV in cell culture with an IC50 of around 2 micromolar. Resistance development was slow and resulted in the HIV RT mutant 184V. FLG has been evaluated in DHBV-infected ducklings. Inhibition of DHBV-DNA in serum was seen at dosages down to 0.3-1 mg/kg/day. FLG was highly effective when evaluated in SIV-infected monkeys, a model for HIV infection. Toxicity studies in mice, ducks and cynomologus monkeys did not show any significant adverse effect during or after the treatment period 4+4 weeks. Studies in cynomolgus monkeys showed an oral bioavailability of FLG of 4% and a oral plasma half-life of 1.2 hours. Synthesis of new prodrugs of FLG have improved the oral bioavailability to about 50%. An FLG prodrug has been scheduled for clinical development.
Publication Types:
Keywords:
- Acyclovir
- Animals
- Antiviral Agents
- Biomedical Research
- Ducks
- Hepatitis B Virus, Duck
- Hepatitis B virus
- Hepatocytes
- In Vitro
- Lamivudine
- Mice
- Research
- penciclovir
Other ID:
UI: 102236613
From Meeting Abstracts