Effect of oral administration of emtricitabine on woodchuck hepatitis virus replication in chronically infected woodchucks

被引:41
作者
Korba, BE
Schinazi, RF
Cote, P
Tennant, BC
Gerin, JL
机构
[1] Georgetown Univ, Med Ctr, Div Mol Virol & Immunol, Rockville, MD 20850 USA
[2] Emory Univ, Vet Adm Hosp, Decatur, GA USA
[3] Cornell Univ, Coll Vet Med, Ithaca, NY 14853 USA
关键词
D O I
10.1128/AAC.44.6.1757-1760.2000
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Emtricitabine [(-)FTC] [(-)-beta-2',3'-dideoxy-5-fluoro-3'-thiacytidine] has been shown to be an effective inhibitor of hepatitis B virus (HBV) in cell culture, with a potency and selectivity that are essentially identical to those of lamivudine. The antiviral activity of oral administration of (-)FTC against WHV replication in chronically infected woodchucks, an established and predictive model for antiviral therapy against HBV, was examined in a placebo-controlled study. (-)FTC significantly reduced viremia and intrahepatic WHV replication in a dose-dependent manner that was comparable to the antiviral activity of lamivudine observed in previous studies conducted by our laboratories. No effect on the levels of hepatic WHV RNA or the levels of woodchuck hepatitis surface antigen or anti-woodchuck hepatitis surface and core antibodies in the serum of the treated animals was observed. No evidence of drug-related toxicity was observed in any of the animals treated.
引用
收藏
页码:1757 / 1760
页数:4
相关论文
共 21 条
[1]   PHARMACOKINETICS OF 2',3'-DIDEOXY-5-FLUORO-3'-THIACYTIDINE IN RATS [J].
ABOBO, CV ;
NI, L ;
SCHINAZI, RF ;
LIOTTA, DC ;
BOUDINOT, FD .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1994, 83 (01) :96-99
[2]  
Cote Paul J., 1993, Viral Immunology, V6, P161, DOI 10.1089/vim.1993.6.161
[3]   In vivo antiviral activity and pharmacokinetics of (-)-cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine in woodchuck hepatitis virus-infected woodchucks [J].
Cullen, JM ;
Smith, SL ;
Davis, MG ;
Dunn, SE ;
Botteron, C ;
Cecchi, A ;
Linsey, D ;
Linzey, D ;
Frick, L ;
Paff, MT ;
Goulding, A ;
Biron, K .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1997, 41 (10) :2076-2082
[4]   INHIBITION OF HEPATITIS-B VIRUS IN TISSUE-CULTURE BY ALPHA-INTERFERON [J].
DAVIS, MG ;
JANSEN, RW .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1994, 38 (12) :2921-2924
[5]   THE ANTI-HEPATITIS-B VIRUS ACTIVITIES, CYTOTOXICITIES, AND ANABOLIC PROFILES OF THE (-) AND (+) ENANTIOMERS OF CIS-5-FLUORO-1-[2-(HYDROXYMETHYL)-1,3-OXATHIOLAN-5-YL]CYTOSINE [J].
FURMAN, PA ;
DAVIS, M ;
LIOTTA, DC ;
PAFF, M ;
FRICK, LW ;
NELSON, DJ ;
DORNSIFE, RE ;
WURSTER, JA ;
WILSON, LJ ;
FYFE, JA ;
TUTTLE, JV ;
MILLER, WH ;
CONDREAY, L ;
AVERETT, DR ;
SCHINAZI, RF ;
PAINTER, GR .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1992, 36 (12) :2686-2692
[6]  
Ganem D., 1996, FIELDS VIROLOGY, P2703
[7]  
Gerin J L, 1990, Gastroenterol Jpn, V25 Suppl 2, P38
[8]   ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS ACTIVITIES OF THE BETA-L ENANTIOMER OF 2',3'-DIDEOXYCYTIDINE AND ITS 5-FLUORO DERIVATIVE IN-VITRO [J].
GOSSELIN, G ;
SCHINAZI, RF ;
SOMMADOSSI, JP ;
MATHE, C ;
BERGOGNE, MC ;
AUBERTIN, AM ;
KIRN, A ;
IMBACH, JL .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1994, 38 (06) :1292-1297
[9]   Pharmacodynamics of (-)-β-2′,3′-dideoxy-3′-thiacytidine in chronically virus-infected woodchucks compared to its pharmacodynamics in humans [J].
Hurwitz, SJ ;
Tennant, BC ;
Korba, BE ;
Gerin, JL ;
Schinazi, RF .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1998, 42 (11) :2804-2809
[10]  
KORBA B, IN PRESS HEPATOLOGY