Pegylation of protein drugs and pegylated interferon modifying pharmacokinetic and pharmacodynamic properties

摘要

Pegylation was developed in the 1970s to enhance the delivery of therapeutic proteins. The chemical attachment of PEG to proteins produces modifying pharmacokinetic and pharmacodynamic benefits, including enhanced plasma half-life, lower toxicity, and increased drug stability and solubility. Pegylated protein can increase its therapeutic efficacy by reducing the ability of the immunone system to decte and mount an attack on the compound. Some pegylated protein products such as pegademase, pegaspargase and pegylated interferon-alpha (pegasys), are currently approved for clinical use. Based on available data, it is obvious that both pegylated interferon- alpha-2a and pegylated interferon- alpha-2b have superior efficacy for the treatment of chronic hepatitis C virus when compared with unmodified interferon- alpha -2a and interferon- alpha-2b, respectively. The higher molecular weight, branched pegylated mterferon- alpha -2a may have a better pharmacokinetic and pharmacodynamic properties than the lower molecular weight interferon- alpha-2b. Clearly, pegylated therapeutic proteins in general is valuable, and pegylated interferon promises to increase treatment success in patients with chronic hepatitis C virus infection.