摘要
Background/Aims:To compare the pharmacokinetics,pharmacodynamics,and antiviral activity of peginterferon alfa-2b and peginterferon alfa-2a in patients with chronic hepatitis C virus genotype 1.Methods:Thirty-six patients were randomised to peginterferon alfa-2b(1.5 μ g/kg/week) or peginterferon alfa-2a(180 μ g/week) for 4 weeks,then in combination with ribavirin(13 mg/kg/day) for a further 4 weeks.The pharmacokinetic profile of both peginterferons,mRNA expression of a selected group of interferon-induced gene transcripts,and serum HCV-RNA levels were assessed.Results:Patients receiving peginterferon alfa-2b had significantly greater up-regul-ation of interferon-alfa response genes compared with those receiving peginterferon alfa-2a.Correspondingly,patients treated with peginterferon alfa-2b also had a significantly greater log10 maximum and log10 time-weighted average decrease in serum HCV-RNA.A greater proportion of peginterferon alfa-2b patients achieved a ≥ 2.0 log10 reduction in serum HCV-RNA levels by week 8(72% vs 44% of peginterferon alfa-2a patients,P = 0.09) .There was an approximately 16-fold greater exposure to peginterferon in the serum of patients treated with peginterferon alfa-2a.Conclusions:These findings suggest that the biological activity,measured by early interferon-induced gene transcripts and early antiviral responsiveness,may have been greater in patients treated with peginterferon alfa-2b despite their lower exposure to the drug compared with patients treated with peginterferon alfa-2a.
Background/Aims:To compare the pharmacokinetics,pharmacodynamics,and antiviral activity of peginterferon alfa-2b and peginterferon alfa-2a in patients with chronic hepatitis C virus genotype 1.Methods:Thirty-six patients were randomised to peginterferon alfa-2b(1.5 μ g/kg/week) or peginterferon alfa-2a(180 μ g/week) for 4 weeks,then in combination with ribavirin(13 mg/kg/day) for a further 4 weeks.The pharmacokinetic profile of both peginterferons,mRNA expression of a selected group of interferon-induced gene transcripts,and serum HCV-RNA levels were assessed.Results:Patients receiving peginterferon alfa-2b had significantly greater up-regul-ation of interferon-alfa response genes compared with those receiving peginterferon alfa-2a.Correspondingly,patients treated with peginterferon alfa-2b also had a significantly greater log10 maximum and log10 time-weighted average decrease in serum HCV-RNA.A greater proportion of peginterferon alfa-2b patients achieved a ≥ 2.0 log10 reduction in serum HCV-RNA levels by week 8(72% vs 44% of peginterferon alfa-2a patients,P = 0.09) .There was an approximately 16-fold greater exposure to peginterferon in the serum of patients treated with peginterferon alfa-2a.Conclusions:These findings suggest that the biological activity,measured by early interferon-induced gene transcripts and early antiviral responsiveness,may have been greater in patients treated with peginterferon alfa-2b despite their lower exposure to the drug compared with patients treated with peginterferon alfa-2a.
