Polyethylene glycol (PEG) moieties can be attached to proteins to improve their pharmacological properties. Variables such as the molecular weight and conformation of PEG chains have a bearing on the conjugate’s properties and should be considered when developing pegylated proteins with desired characteristics. Recombinant interferon (IFN) alfa has been used, with limited success, to treat patients infected with hepatitis C virus. The recommended thrice-weekly administration of IFN alfa does not maintain sustained plasma concentrations of the drug, thereby adversely affecting the potential virological response. Pegylation alters the pharmacokinetic properties of IFN alfa and allows for once-weekly administration. Pegylated IFNs contain either linear PEG chains of small molecular weight, as is pegylated IFN alfa-2b (12 kD), or larger branched moieties, as in pegylated IFN alfa-2a (40 kD). There are pharmacokinetic and pharmacodynamic differences between the two IFNs. The much-increased sustained virological response rates observed with pegylated IFN alfa-2a (40 kD) and pegylated IFN alfa-2b (12 kD) support the rationale for pegylation of IFN.
KEYWORDS
Pegylated interferon - polyethylene glycol - hepatitis C - pharmacokinetics - pharmacodynamics
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K. Rajender ReddyM.D.
GI Division, 3 Ravdin, Hospital of the University of Pennsylvania
3400 Spruce Street
Philadelphia, PA 19104
eMail: rajender.reddy@uphs.upenn.edu
