Modelling of early viral kinetics and pegylated interferon-α2b pharmacokinetics in patients with HBeAg-positive chronic hepatitis B

Martijn J. Ter Borg, Bettina E. Hansen, Eva Herrmann, Stefan Zeuzem, Yilmaz Cakaloglu, Selim Karayalcin, Robert Flisiak, Annemarie Van't Veen, Robert A. De Man, Solko W. Schalm, Harry L.A. Janssen*, Bart L. Haagmans

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Scopus)

Abstract

Background: Pegylated interferon α2b (PEG-IFN-α2b) is effective for the treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, although its mechanism of action remains unclear. HBeAg loss is achieved in 36% of patients after one year of PEG-IFN-α2b treatment and combination therapy with lamivudine is not superior to PEG-IFN-α2b monotherapy. Methods: Early pharmacokinetics and viral kinetics were analysed in patients treated for 52 weeks with PEG-IFN-α2b with or without lamivudine. Results: After 4 weeks of treatment, there was a median viral decline of 2.94 log 10 copies/ml in those treated with PEG-IFN-α2b and lamivudine and only 0.45 log10 copies/ml in the PEG-IFN-α2b monotherapy group. Peak PEG-IFN-α2b levels were reached approximately one day after administration and subsequently declined exponentially, consistent with a viral load rebound near to baseline levels at the end of the dosing period in most patients receiving PEG-IFN-α2b monotherapy. Modelling of pharmacokinetics and viral kinetics data in this group revealed that viral load was minimal 3.6 days after PEG-IFN-α2b administration, the mean maximal and mean antiviral effectiveness was 70% and 48% with a mean infected cell loss rate of 0.07 per day, while no significant biphasic decline was observed. Conclusions: PEG-IFN-α2b induces a sustained response in a considerable number of patients despite limited direct antiviral activity during the first weeks of antiviral therapy.

Original languageEnglish
Pages (from-to)1285-1294
Number of pages10
JournalAntiviral Therapy
Volume12
Issue number8
DOIs
Publication statusPublished - Nov 2007

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