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  1. Article ; Online: Endogenous IFNλ in viral hepatitis patients.

    de Groen, Rik A / Mcphee, Fiona / Friborg, Jacques / Janssen, Harry L A / Boonstra, André

    Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research

    2014  Volume 34, Issue 7, Page(s) 552–556

    Abstract: Besides type I interferons (IFNs), type III IFNs, including IFNλ1 (interleukin-29 [IL-29]), possess potent antiviral activity. In patients infected with the hepatitis C virus (HCV), it has been demonstrated that viral clearance is associated with genetic ...

    Abstract Besides type I interferons (IFNs), type III IFNs, including IFNλ1 (interleukin-29 [IL-29]), possess potent antiviral activity. In patients infected with the hepatitis C virus (HCV), it has been demonstrated that viral clearance is associated with genetic variation near the IFNλ3 (IL-28B) gene. The rapid influx of research being conducted on this family of cytokines has led to several inconsistencies and controversies, including the possible correlation of serum cytokine levels with disease in chronic viral hepatitis patients. In a detailed study, well-characterized cohorts of patients with HBV and HCV were evaluated with 3 different immunoassays, and no differences in the levels of serum IFNλ were observed between patient groups, disease stages, or clinical parameters.
    MeSH term(s) Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cohort Studies ; Female ; Hepatitis B, Chronic/blood ; Hepatitis B, Chronic/physiopathology ; Hepatitis C, Chronic/blood ; Hepatitis C, Chronic/physiopathology ; Humans ; Interferon-gamma/blood ; Male ; Middle Aged
    Chemical Substances Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2014-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1226675-9
    ISSN 1557-7465 ; 1079-9907
    ISSN (online) 1557-7465
    ISSN 1079-9907
    DOI 10.1089/jir.2013.0068
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  2. Article ; Online: Preclinical Pharmacokinetics and In Vitro Metabolism of Asunaprevir (BMS-650032), a Potent Hepatitis C Virus NS3 Protease Inhibitor.

    Mosure, Kathleen W / Knipe, Jay O / Browning, Marc / Arora, Vinod / Shu, Yue-Zhong / Phillip, Thomas / Mcphee, Fiona / Scola, Paul / Balakrishnan, Anand / Soars, Matthew G / Santone, Kenneth / Sinz, Michael

    Journal of pharmaceutical sciences

    2015  Volume 104, Issue 9, Page(s) 2813–2823

    Abstract: Asunaprevir (ASV; BMS-650032), a low nanomolar inhibitor of the hepatitis C virus (HCV) NS3 protease, is currently under development, in combination with other direct-acting antiviral (DAA) agents for the treatment of chronic HCV infection. Extensive ... ...

    Abstract Asunaprevir (ASV; BMS-650032), a low nanomolar inhibitor of the hepatitis C virus (HCV) NS3 protease, is currently under development, in combination with other direct-acting antiviral (DAA) agents for the treatment of chronic HCV infection. Extensive nonclinical and pharmacokinetic studies have been conducted to characterize the ADME properties of ASV. ASV has a moderate to high clearance in preclinical species. In vitro reaction phenotyping studies demonstrated that the oxidative metabolism of ASV is primarily mediated via CYP3A4; however, studies in bile-duct cannulated rats and dogs suggest that biliary elimination may contribute to overall ASV clearance. ASV is shown to have hepatotropic disposition in all preclinical species tested (liver to plasma ratios >40). The translation of in vitro replicon potency to clinical viral load decline for a previous lead BMS-605339 was leveraged to predict a human dose of 2 mg BID for ASV. Clinical drug-drug interaction (DDI) studies have shown that at therapeutically relevant concentrations of ASV the potential for a DDI is minimal. The need for an interferon free treatment combined with ASV's initial clinical trial data support development of ASV as part of a fixed dose combination for the treatment of patients chronically infected with HCV genotype 1.
    MeSH term(s) ATP-Binding Cassette, Sub-Family B, Member 1/antagonists & inhibitors ; ATP-Binding Cassette, Sub-Family B, Member 1/metabolism ; Animals ; Antiviral Agents/pharmacokinetics ; Bile/metabolism ; Biological Availability ; Cytochrome P-450 CYP3A/metabolism ; Cytochrome P-450 Enzyme Inhibitors/pharmacology ; Dogs ; Hepacivirus/drug effects ; Hepacivirus/enzymology ; Hepatocytes/metabolism ; Humans ; Isoquinolines/pharmacokinetics ; Liver/metabolism ; Macaca fascicularis ; Male ; Mice ; Microsomes, Liver/metabolism ; Oxidation-Reduction ; Protease Inhibitors/pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Sulfonamides/pharmacokinetics ; Viral Nonstructural Proteins/antagonists & inhibitors
    Chemical Substances ATP-Binding Cassette, Sub-Family B, Member 1 ; Antiviral Agents ; Cytochrome P-450 Enzyme Inhibitors ; Isoquinolines ; NS3 protein, hepatitis C virus ; Protease Inhibitors ; Sulfonamides ; Viral Nonstructural Proteins ; Cytochrome P-450 CYP3A (EC 1.14.14.1) ; asunaprevir (S9X0KRJ00S)
    Language English
    Publishing date 2015-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3151-3
    ISSN 1520-6017 ; 0022-3549
    ISSN (online) 1520-6017
    ISSN 0022-3549
    DOI 10.1002/jps.24356
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Uf I Zs.50: Show issues Location:
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