کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6105882 | 1211154 | 2011 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Research ArticleAntiviral activity, safety, and pharmacokinetics of danoprevir/ritonavir plus PEG-IFN α-2a/RBV in hepatitis C patients Research ArticleAntiviral activity, safety, and pharmacokinetics of danoprevir/ritonavir plus PEG-IFN α-2a/RBV in hepatitis C patients](/preview/png/6105882.png)
Background & AimsDanoprevir (RG7227; ITMN-191) is a potent inhibitor of the HCV NS3/4A serine protease. The aims of this double-blind, placebo-controlled, multiple-ascending dose phase Ib study were to evaluate safety, tolerability, antiviral activity, resistance, and pharmacokinetics of once- and twice-daily danoprevir in the presence of low-dose ritonavir (danoprevir/r) and in combination with peginterferon alfa-2a (40KD)/ribavirin in treatment-naive HCV genotype 1 patients.MethodsThirty eligible patients were enrolled into three cohorts and treated with danoprevir/r or placebo/r all in combination with peginterferon alfa-2a (40KD)/ribavirin for 15Â days. Cohort 1 received danoprevir/r at 100/100Â mg twice daily; Cohort 2 200/100Â mg once daily; and Cohort 3 200/100Â mg twice daily.ResultsThe median reductions in HCV RNA from baseline after 14Â days of treatment (day 15) were -5.1, -4.8, and -4.6 log10Â IU/ml in Cohorts 1, 2, and 3, respectively, and -2.7 log10 in placebo/r and peginterferon alfa-2a (40KD)/ribavirin recipients. Viral breakthrough was not observed in any patient. On day 15, HCV RNA was undetectable (<15Â IU/ml) in 6/9 (67%), 4/8 (50%), and 8/8 (100%) patients in Cohorts 1, 2, and 3, respectively. When co-administered with low dose ritonavir, danoprevir concentrations reached a steady state between 6 to 10Â days of dosing. Danoprevir exposures increased more than dose proportionally between 100/100Â mg and 200/100Â mg. Danoprevir/r plus peginterferon alfa-2a (40KD)/ribavirin was well-tolerated with no safety-related discontinuations.ConclusionsDanoprevir/r plus peginterferon alfa-2a (40KD)/ribavirin provides profound and robust reductions in serum HCV RNA, at substantially lower systemic exposures compared to those observed with higher doses of danoprevir in the absence of ritonavir. These results support further studies of danoprevir/r.
Journal: Journal of Hepatology - Volume 55, Issue 5, November 2011, Pages 972-979