Modelling of early viral kinetics and pegylated interferon-alpha2b pharmacokinetics in patients with HBeag-positive chronic hepatitis B.
BACKGROUND
Pegylated interferon alpha2b (PEG-IFN-alpha(2b) 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-alpha2b treatment and combination therapy with lamivudine is not superior to PEG-IFN-alpha2b monotherapy.


METHODS
Early pharmacokinetics and viral kinetics were analysed in patients treated for 52 weeks with PEG-IFN-alpha2b with or without lamivudine.


RESULTS
After 4 weeks of treatment, there was a median viral decline of 2.94 log10 copies/ml in those treated with PEG-IFN-alpha2b and lamivudine and only 0.45 log10 copies/ml in the PEG-IFN-alpha2b monotherapy group. Peak PEG-IFN-alpha2b 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-alpha2b monotherapy. Modelling of pharmacokinetics and viral kinetics data in this group revealed that viral load was minimal 3.6 days after PEG-IFN-alpha2b 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-alpha2b induces a sustained response in a considerable number of patients despite limited direct antiviral activity during the first weeks of antiviral therapy.
ter Borg
Martijn J
MJ
Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.
Hansen
Bettina E
BE
Herrmann
Eva
E
Zeuzem
Stefan
S
Cakaloglu
Yilmaz
Y
Karayalcin
Selim
S
Flisiak
Robert
R
van' t Veen
Annemarie
A
de Man
Robert A
RA
Schalm
Solko W
SW
Janssen
Harry La
HL
Haagmans
Bart L
BL
D000328:Adult; D000998:Antiviral Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004279:DNA, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008954:Models, Biological; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019562:Viral Load
D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b