期刊
ANTIVIRAL RESEARCH
卷 54, 期 2, 页码 69-78出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/S0166-3542(01)00216-9
关键词
antiviral activity; animal models; human hepatitis B virus; transgenic mice
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 close-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 shogun rapid absorption. a bioavailability of 30% and dose-proportional plasma concentrations. We conclude that BAY 41-4109 is a new anti-HBV drug candidate. (C) 2002 Elsevier Science B.V. All rights, reserved.
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