ABSTRACT
The attachment of a polyethylene glycol (PEG) polymer to a protein or peptide is becoming
increasingly common within the pharmaceutical industry as a way of altering the activity
of the parent molecule. Significant improvements in biological activity with PEG molecules
have been seen with several licensed drugs, allowing for product life cycle management,
as well as with experimental compounds in development that have pharmaceutical properties
making them suitable candidates for pegylation. Among the various disease states that
have been targeted for the study of drugs incorporating pegylation technology, the
treatment of chronic hepatitis C with interferon-based compounds offers significant
potential for clinical impact. Two separate compounds, peginterferon alfa-2a (PEGASYS(r)) and peginterferon alfa-2b (PEG-Intron(r)) are now both approved for use alone and in combination with ribavirin for the treatment
of chronic hepatitis C. However, the different PEG moieties attached to the native
protein, the site of attachment and the type of bond involved lead to vast differences
with respect to the pharmacokinetics (including absorption, biodistribution, metabolism
and elimination) and pharmacodynamics of these two compounds. This article discusses
the differences that exist between these compounds, which may lead to different clinical
profiles for their use in the treatment of patients with hepatitis C.
KEYWORDS
Pegylation - interferons - PEGASYS(r)
- PEG-Intron(r)
- pharmacokinetics
