title: A new sustained-release preparation of human growth hormone and its pharmacokinetic, pharmacodynamic and safety profile.
abstract: OBJECTIVE
  Adult GH replacement is currently given by daily subcutaneous (sc) injections. Recently, sustained-release (SR) preparations of GH have been developed, the preparations being characterized by a dominant early release, resulting in supraphysiological early GH peaks, and a rapid decline thereafter. We present data on a new SR GH preparation.
  
  
  METHODS
  Phase I/II study of hGH-Biosphere(R) (SkyePharma AB, Malmo, Sweden), a new SR preparation of recombinant human GH in amylopectin microspheres coated with polylactide-coglycolide.
  
  
  METHODS
  Eight adults with severe, untreated GH deficiency (stimulated GH peaks between < 1 and 1.7 microg/l), aged 36.1 years (range 22-49 years) in good general health.
  
  
  METHODS
  Pharmacokinetic (PK), pharmacodynamic (PD) and safety data over a period of 28 days.
  
  
  RESULTS
  The systemic and local tolerability of the drug was satisfactory, and no serious adverse events occurred. PK analysis showed a smaller early serum hGH peak followed by a broad sustained second peak of hGH (C(max) 1.20 microg/l at 7.2 days), and hGH levels were maintained above baseline for at least 14 days. The mean GH level never exceeded 1.1 microg/l, making the GH fluctuations comparable to continuous sc infusion. Resultant IGF-I concentrations were characterized by sustained elevation at a level near C(max) of 103 microg/l (at t(max) of 9.7 days), equal to an SD score of +0.8. IGF-I generation per administered GH was more efficient compared with reports of other SR preparations.
  
  
  CONCLUSIONS
  hGH-Biosphere(R) is a well-tolerated SR GH preparation with superior efficacy in achieving target IGF-I levels without causing supraphysiological GH concentrations. Our data suggest the suitability of this preparation for longer-term trials in adults with injection frequencies of no more than once every 2-3 weeks.
authors.affiliation: Department of Endocrinology, Christie Hospital, Manchester, UK. andreas.jostel@christie-tr.nwest.nhs.uk
authors.forename: Andreas
authors.initials: A
authors.lastname: Jostel
authors.forename: Annice
authors.initials: A
authors.lastname: Mukherjee
authors.forename: Jan
authors.initials: J
authors.lastname: Alenfall
authors.forename: Linda
authors.initials: L
authors.lastname: Smethurst
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Shalet
mesh_terms: D000328:Adult; D019540:Area Under Curve; D003692:Delayed-Action Preparations; D004890:Erythema / Q000139:chemically induced; D005260:Female; D006130:Growth Disorders / Q000188:drug therapy*; D013006:Growth Hormone / Q000097:blood / Q000172:deficiency; D019382:Human Growth Hormone / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007273:Injections, Intramuscular; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D014581:Urticaria / Q000139:chemically induced
chemical_list: D003692:Delayed-Action Preparations; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone