Pharmacokinetics of pegylated interferons: what is misleading?

Abstract

Available pegylated interferon (PEG-IFN) products confer enhanced therapeutic efficacy when compared with their IFN counterparts, and the added convenience of once-weekly dosing with no novel toxicities. PEG optimises the action of the IFNs by decreasing clearance rates, thereby allowing serum concentrations to remain constant over the dosing period. The length and shape of each PEG moiety are crucial in determining the effect on pharmacokinetic and pharmacodynamic properties. In vitro activity decreases with increasing PEG size, therefore the reduction of potency at the molecular receptor should be compensated by the prolonged residence in blood, or by the higher total drug exposure. Moreover, in hepatitis C, viral suppression in blood alone may not be enough, HCV reservoirs outside the blood may play a role in HCV persistence, therefore drugs with a low volume of distribution offer much less chance for infiltrating extravascular tissue and may explain its higher relapse rate. The case of PEG-IFNs for use in the treatment of chronic hepatitis C clearly demonstrates the potential for different characteristics among PEG conjugates.