title: Novel effects with polyethylene glycol modified pharmaceuticals.
abstract: Proteins undergo extensive hydrolysis in the gastrointestinal tract and have short circulating half-lives in the blood. For optimal clinical efficacy, therefore, they must be given by daily injections. Attaching a polyethylene glycol (PEG) moiety (pegylation) improves the pharmacokinetic and pharmacodynamic profiles of proteins. Pegfilgrastim (pegylated filgrastim) has a longer half-life than unmodified filgrastim and, when administered as a single dose, has been shown to be at least as efficacious as daily filgrastim. Because of its reduced renal clearance, the elimination of pegfilgrastim is predominantly neutrophil-mediated, so its clearance is self-regulated. In addition, pegfilgrastim can be administered at a fixed dose instead of in weight-based doses. For these reasons, pegfilgrastim can potentially increase patient adherence and acceptance of treatment, thus having a beneficial effect on their quality of life. Furthermore, treatment is likely to cost less because of the reduced need for medical interventions. Similarly, pegylated liposomal doxorubicin has a longer half-life than unmodified doxorubicin and has been shown, because of its reduced reticuloendothelial system clearance, to produce higher concentrations of doxorubicin in tumours and to have greater clinical efficacy than doxorubicin in the treatment of some solid tumours. Pegylated liposomal doxorubicin is also associated with less myelosuppression and febrile neutropenia.
authors.affiliation: Department of Pharmacy, Duke University Medical Center, Box 3089, Durham, NC 27710, USA. sally.yowell@duke.edu
authors.forename: S L
authors.initials: SL
authors.lastname: Yowell
authors.forename: S
authors.initials: S
authors.lastname: Blackwell
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004355:Drug Stability; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D008081:Liposomes; D008657:Metabolic Clearance Rate; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy; D010342:Patient Acceptance of Health Care; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D011994:Recombinant Proteins
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D004317:Doxorubicin; D000069585:Filgrastim