title: Polyethylene glycol-conjugated growth hormone-releasing hormone is long acting and stimulates GH in healthy young and elderly subjects.
abstract: OBJECTIVE
  The clinical use of growth hormone-releasing hormone (GHRH) is limited by its short half-life. Polyethylene glycol-conjugated GHRH (PEG-GHRH) was developed to provide increased stability compared with the currently available GHRH(1-29). This study aimed to evaluate the safety, tolerability and pharmacodynamics of PEG-GHRH.
  
  
  METHODS
  PEG-GHRH was administered by subcutaneous injection to young healthy men (n = 12) and elderly men and women (aged > 60 years; n = 20).
  
  
  RESULTS
  In both groups, administration of PEG-GHRH generated a clear increase in circulating GH compared with placebo. Following single-dose (0.25, 0.5, 2 or 4 mg) administration to young subjects, the effect persisted for 12 h, but a sustained increase was observed on repeated administration to the elderly. Serum insulin-like growth factor-I also increased in response to PEG-GHRH treatment. Injection-site reactions were more frequent with PEG-GHRH compared with placebo, but these were mild and transient; other adverse events were similar to those observed after placebo. Some impairment of glucose tolerance was observed in the elderly following repeated administration of PEG-GHRH. Antibodies to GHRH were not observed.
  
  
  CONCLUSIONS
  PEG-GHRH offers the possibility of less frequent dosing compared with GHRH. This possibility deserves further clinical testing.
authors.affiliation: Serono International S.A., 15 bis chemin des Mines, Genèva, Switzerland. alain.munafo@serono.com
authors.forename: A
authors.initials: A
authors.lastname: Munafo
authors.forename: T X Q
authors.initials: TX
authors.lastname: Nguyen
authors.forename: O
authors.initials: O
authors.lastname: Papasouliotis
authors.forename: H
authors.initials: H
authors.lastname: Lécuelle
authors.forename: A
authors.initials: A
authors.lastname: Priestley
authors.forename: M O
authors.initials: MO
authors.lastname: Thorner
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019382:Human Growth Hormone / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D017337:Sermorelin / Q000008:administration & dosage
chemical_list: D019382:Human Growth Hormone; D011092:Polyethylene Glycols; D007334:Insulin-Like Growth Factor I; D017337:Sermorelin; D013007:Growth Hormone-Releasing Hormone