A new sustained-release preparation of human growth hormone and its pharmacokinetic, pharmacodynamic and safety profile.

2.50
Hdl Handle:
http://hdl.handle.net/10541/74882
Title:
A new sustained-release preparation of human growth hormone and its pharmacokinetic, pharmacodynamic and safety profile.
Authors:
Jostel, Andreas; Mukherjee, Annice; Alenfall, Jan; Smethurst, Linda E; Shalet, Stephen M
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. DESIGN: 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. PATIENTS: 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. 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 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. CONCLUSION: 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.
Affiliation:
Department of Endocrinology, Christie Hospital, Manchester, UK. andreas.jostel@christie-tr.nwest.nhs.uk
Citation:
A new sustained-release preparation of human growth hormone and its pharmacokinetic, pharmacodynamic and safety profile. 2005, 62 (5):623-7 Clin. Endocrinol.
Journal:
Clinical Endocrinology
Issue Date:
May-2005
URI:
http://hdl.handle.net/10541/74882
DOI:
10.1111/j.1365-2265.2005.02271.x
PubMed ID:
15853836
Type:
Article
Language:
en
ISSN:
0300-0664
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorJostel, Andreas-
dc.contributor.authorMukherjee, Annice-
dc.contributor.authorAlenfall, Jan-
dc.contributor.authorSmethurst, Linda E-
dc.contributor.authorShalet, Stephen M-
dc.date.accessioned2009-07-22T10:00:12Z-
dc.date.available2009-07-22T10:00:12Z-
dc.date.issued2005-05-
dc.identifier.citationA new sustained-release preparation of human growth hormone and its pharmacokinetic, pharmacodynamic and safety profile. 2005, 62 (5):623-7 Clin. Endocrinol.en
dc.identifier.issn0300-0664-
dc.identifier.pmid15853836-
dc.identifier.doi10.1111/j.1365-2265.2005.02271.x-
dc.identifier.urihttp://hdl.handle.net/10541/74882-
dc.description.abstractOBJECTIVE: 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(R) (SkyePharma AB, Malmo, 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 microg/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 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. CONCLUSION: 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.en
dc.language.isoenen
dc.subject.meshAdult-
dc.subject.meshArea Under Curve-
dc.subject.meshDelayed-Action Preparations-
dc.subject.meshErythema-
dc.subject.meshFemale-
dc.subject.meshGrowth Disorders-
dc.subject.meshGrowth Hormone-
dc.subject.meshHuman Growth Hormone-
dc.subject.meshHumans-
dc.subject.meshInjections, Intramuscular-
dc.subject.meshInsulin-Like Growth Factor I-
dc.subject.meshMale-
dc.subject.meshMicrospheres-
dc.subject.meshMiddle Aged-
dc.subject.meshRecombinant Proteins-
dc.subject.meshUrticaria-
dc.titleA new sustained-release preparation of human growth hormone and its pharmacokinetic, pharmacodynamic and safety profile.en
dc.typeArticleen
dc.contributor.departmentDepartment of Endocrinology, Christie Hospital, Manchester, UK. andreas.jostel@christie-tr.nwest.nhs.uken
dc.identifier.journalClinical Endocrinologyen
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