Effects of pharmaceutical PEGylation on drug metabolism and its clinical concerns.

INTRODUCTION: PEGylation refers to covalent conjugation of one or more polyethylene glycol chains to a drug molecule. It also refers to formulation of a drug into PEGylated drug-delivery vehicles in pharmacy. It is well-known that PEGylation can greatly influence the pharmacokinetics and pharmacodynamics of drugs. AREAS COVERED: This article describes the importance of PEGylation in drug development and research. The impact of PEGylation on drug metabolism and the clinical safety of PEGylated drugs (or formulations) are also discussed. Information and data from the literature were collected, analyzed and summarized. EXPERT OPINION: PEGylation is an effective approach to potentiate drugs with undesirable properties. Currently, PEGylation has penetrated into every field of pharmaceutical practice, involving biomacromolecules, small drugs and drug delivery systems. Efficacy enhancement is attained through modification of the pharmacokinetics and toxicity profiles of parent drugs. As a result of PEGylation, the drugs tend to display enhanced solubility, prolonged circulatory time and reduced immunogenicity/antigenicity. The bottleneck of PEGylation is how to break through the limitation of chemical conjugation and to properly preserve the pharmacological activity of the drug. PEGylated formulation is an area deserving more attention in terms of systemic delivery of insoluble small drugs.