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A new sustained‐release preparation of human growth hormone and its pharmacokinetic, pharmacodynamic and safety profile
Author(s) -
Jostel Andreas,
Mukherjee Annice,
Alenfall Jan,
Smethurst Linda,
Shalet Stephen M.
Publication year - 2005
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2005.02271.x
Subject(s) - pharmacokinetics , tolerability , pharmacodynamics , medicine , adverse effect , growth hormone , endocrinology , human growth hormone , somatropin , chemistry , hormone
Summary 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. Design Phase I/II study of hGH‐Biosphere® (SkyePharma AB, Malmö, Sweden), a new SR preparation of recombinant human GH in amylopectin microspheres coated with polylactide‐coglycolide. Patients Eight adults with severe, untreated GH deficiency (stimulated GH peaks between < 1 and 1·7 µg/l), aged 36·1 years (range 22–49 years) in good general health. Measurements 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 µg/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 µg/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 µg/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. Conclusion hGH‐Biosphere® 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.