Pegylation: engineering improved pharmaceuticals for enhanced therapy.
Conjugating biomolecules with polyethylene glycol (PEG), a process known as pegylation, is now an established method for increasing the circulating half-life of protein and liposomal pharmaceuticals. Polyethylene glycols are nontoxic water-soluble polymers that, owing to their large hydrodynamic volume, create a shield around the pegylated drug, thus protecting it from renal clearance, enzymatic degradation, and recognition by cells of the immune system. Agent-specific pegylation methods have been used in recent years to produce pegylated drugs that have biologic activity that is the same as, or greater than, that of the parent drug. These agents have distinct in vivo pharmacokinetic and pharmacodynamic properties, as exemplified by the self-regulated clearance of pegfilgrastim, the prolonged absorption half-life of pegylated interferon alpha-2a, and the altered tolerability profile of pegylated liposomal doxorubicin. Pegylated agents have dosing schedules that are more convenient and more acceptable to patients, and this can have a beneficial effect on the quality of life of patients with cancer.
Molineux
G
G
Amgen, Mailstop 15-2-A, One Amgen Center Drive, Thousand Oaks, CA 91320, USA. grahamm@amgen.com
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D001215:Asparaginase / Q000276:immunology / Q000627:therapeutic use; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000493:pharmacokinetics; D008657:Metabolic Clearance Rate; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004337:Drug Carriers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; C042705:pegaspargase; D001215:Asparaginase; D000069585:Filgrastim; C100416:peginterferon alfa-2a