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The decline in hepatitis C viral load on treatment with peginterferon-
-2b is not continuous. The aim of this study was to investigate whether twice weekly dosing of peginterferon-
-2b may improve viral kinetics. Ten interferon-naïve patients with chronic hepatitis C (genotype 1a or b) were randomized to receive either 1.0 µg/kg peginterferon-
-2b once (group A) or twice weekly (group B) for 4 weeks. Viral load and serum concentrations of peginterferon-
-2b were measured. Peginterferon-
-2b reached maximal blood concentrations 24 h after the first dose, followed by a linear decline during the subsequent days. On the day before administration of the next dose, peginterferona-2b was undetectable in nine patients in group A (once weekly dosing). The same pattern was observed during the next 3 weeks of therapy. In group B (twice weekly dosing) peginterferon-
-2b was detectable at any given time point and higher than in group A (P between 0.01 and <0.0001). Viral load decreased in all patients within 2 days after the first dose of peginterferon-
-2b, but increased again on day 3. In group A, it further increased until day 7. A similar pattern was observed in the second week. In contrast, in group B, viral load decreased again on day 4 and remained lower until the end of the study (P < 0.001). To achieve continuous drug exposure and to improve initial viral clearance, peginterferon-
-2b has to be given at least two times weekly.
Pharmacokinetic studies have shown that the concentration-time profile of peginterferon-
-2b is marked by rapid absorption, a prolonged concentration peak and delayed elimination; these pharmacokinetic properties result in measurable serum concentrations for several days after administration. Nevertheless, studies of viral kinetics indicate that administration of peginterferon-
-2b does not result in a continuous decline in viral load in patients infected with hepatitis C virus (HCV) genotype 1 as is seen with daily administration of standard interferon. Results of these studies showed a general rebound of viral levels in blood 2-4 days after administration of peginterferon-
-2b that seemed to be related to the dose (rebound was greater with a higher dose). Because such a rebound is not typical with daily standard interferon or with peginterferon-
-2a (40 kDa), it appears to be related to the pharmacokinetics of peginterferon-
-2b. In fact, the serum concentration of peginterferon-
-2b decreases exponentially with almost undetectable levels on days 6 and 7 after dosing. Thus, the decrease in interferon concentration may result in the rebound of viral levels in blood.
To study the relationship between peginterferon-
-2b concentration and viral load, this prospective randomized study was designed to evaluate patients with chronic hepatitis C infected with HCV genotype 1 treated with 1.0 µg/kg peginterferon-
-2b either once or twice weekly for 4 weeks before starting combination therapy.
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