Inhibition of human hepatitis B virus (HBV) by a novel non-nucleosidic compound in a transgenic mouse model.
Antiviral Res
; 54(2): 69-78, 2002 May.
Article
em En
| MEDLINE
| ID: mdl-12062392
ABSTRACT
BAY 41-4109 is a member of a class of heteroaryl-pyrimidines that was recently identified as potent inhibitors of human hepatitis B virus (HBV) replication. We have investigated the antiviral activity of BAY 41-4109 (methyl (R)-4-(2-chloro-4-fluorophenyl)-2-(3,5-difluoro-2-pyridinyl)-6-methyl-1,4-dihydro-pyrimidine-5-carboxylate) in HBV-transgenic mice (Tg [HBV1.3 fsX(-)3'5']). Bay 41-4109 was administered per os using different schedules (b.i.d. or t.i.d. for up to 28 days) and dosages ranging from 3 to 30 mg/kg. The compound reduced viral DNA in the liver and in the plasma dose-dependently with efficacy comparable to 3TC. In contrast to 3TC-treated mice, we found a reduction of cytoplasmic hepatitis B virus core antigen (HBcAg) in liver sections of BAY 41-4109-treated mice, which indicated a different mode of action. Pharmacokinetic studies in mice have shown rapid absorption, a bioavailability of 30% and dose-proportional plasma concentrations. We conclude that BAY 41-4109 is a new anti-HBV drug candidate.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Piridinas
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Pirimidinas
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Vírus da Hepatite B
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Hepatite B
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Antiviral Res
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Alemanha