Pegylated interferons for the treatment of chronic hepatitis C: pharmacological and clinical differences between peginterferon-alpha-2a and peginterferon-alpha-2b.

Drugs
Graham R Foster

Abstract

Chronic infection with hepatitis C virus (HCV) is a major healthcare problem, affecting an estimated 170 million people worldwide. Interferon-alpha has formed the basis of treatment regimens since the identification of HCV, either alone or in conjunction with the nucleoside analogue ribavirin. The relatively recent introduction of pegylated forms of interferon-alpha, with greater stability and in vivo activity, has substantially improved sustained virological response (SVR) rates compared with unmodified interferon-alpha, with SVR rates of 35-66% when used in conjunction with ribavirin in randomized controlled trials. Two pegylated interferon (peginterferon)-alpha molecules are commercially available for the treatment of chronic hepatitis C, and these differ in the size and nature of the covalently attached polyethylene glycol (PEG) moiety, with resulting differences in pharmacokinetics and in dosing regimens. Peginterferon-alpha-2b has a linear 12 kDa PEG chain covalently attached primarily to histidine-34 of interferon-alpha-2b via an unstable urethane bond that is subject to hydrolysis once injected, releasing native interferon-alpha-2b. The branched, 40 kDa PEG chain of peginterferon-alpha-2a is covalently attached via stab...Continue Reading

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