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.
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 microg regardless of body weight, whereas peginterferon alpha-2b is dosed by body weight at 0.5-1.5 microg/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 microg (n=10) or peginterferon alpha-2b 1.0 microg/kg (n=12). Ribavirin was dosed by body weight at 1000 mg/day (< or = 75kg) or 1200 mg/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.
Bruno
Raffaele
R
Division of Infectious and Tropical Diseases, IRCCS San Matteo Hospital, University of Pavia, Pavia, Italy. r.bruno@smatteo.pv.it
Sacchi
Paolo
P
Maiocchi
Laura
L
Zocchetti
Cristina
C
Ciappina
Valentina
V
Patruno
Savino
S
Filice
Gaetano
G
D000998:Antiviral Agents / Q000627:therapeutic use; D001835:Body Weight; D004337:Drug Carriers / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D011092:Polyethylene Glycols / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use
D000998:Antiviral Agents; D004337:Drug Carriers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a