Area-under-the-curve for peginterferon alpha-2a and peginterferon alpha-2b is not related to body weight in treatment-naive patients with chronic hepatitis C

Abstract: One reason for dosing a drug by body weight is to reduce interpatient variability in clinical response. This study evaluated the relationship between body weight and drug exposure for peginterferon alpha-2a and peginterferon alpha-2b used in combination with ribavirin for treating patients with chronic hepatitis C. These two products are dosed differently: peginterferon alpha-2a is flat-dosed at 180 mu g regardless of body weight, whereas peginterferon alpha-2b is dosed by body weight at 0.5-1.5 mu g/kg. Bodyweight dosing of peginterferon alpha-2b is purported to overcome the adverse effect of increased body weight on sustained virological response. To test this hypothesis, we measured the area-under-the-curve (AUC) for both drugs as part of a previously reported pharmacokinetics study. In total, 22 interferon- naive patients with chronic hepatitis C were treated for 12 weeks. Patients were randomly assigned in a 1:1 ratio to receive once-weekly peginterferon alpha-2a 180 mu g (n=10)or peginterferon alpha-2b 1.0 mu g/kg (n=1 2). Ribavirin was dosed by body weight at 1000mg/day (<= 75kg) or 1200mg/day (> 75 kg). We found no correlation between body weight and AUC for either peginterferon alpha-2a or peginterferon alpha-2b. Considerable interpatient variability in AUC occurred for peginterferon alpha-2a [coefficient of variation (CV): 37.5%] and, despite dosing by body weight, for peginterferon alpha-2b (CV: 36.8%). Thus, there appears to be no rationale for a body-weight dosing regimen for peginterferon alpha-2a, and such dosing does not achieve more consistent AUC measurements in patients receiving peginterferon alpha-2b