Pulmonary delivery of TH9507, a growth hormone releasing factor analogue, in the dog

A modified growth hormone releasing factor (GRF; TH9507), a 44 amino acid peptide analogue of natural human growth hormone releasing factor, is being developed for the treatment of age-associated conditions resulting from diminished growth hormone (GH) secretion. The inhalation route of administrati...

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Bibliographic Details
Published in:International journal of pharmaceutics 2004-05, Vol.276 (1), p.75-81
Main Authors: Jansen, Mendel, Darby, Ian, Abribat, Thierry, Dubreuil, Pascal, Ferdinandi, Eckhardt S, Hardy, John G
Format: Article
Language:English
Subjects:
Absorption
Animals
Area Under Curve
Bioavailability
Biological and medical sciences
Biological Availability
Dogs
Female
General pharmacology
Growth Hormone-Releasing Hormone - analogs & derivatives
Half-Life
hGRF
Injections, Intravenous
Injections, Subcutaneous
Intubation, Intratracheal
Male
Medical sciences
Peptide
Peptides - administration & dosage
Peptides - blood
Peptides - pharmacokinetics
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Powder inhalation
Radioimmunoassay
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Summary:A modified growth hormone releasing factor (GRF; TH9507), a 44 amino acid peptide analogue of natural human growth hormone releasing factor, is being developed for the treatment of age-associated conditions resulting from diminished growth hormone (GH) secretion. The inhalation route of administration is being considered as an alternative to subcutaneous injection. A study was undertaken in dogs to investigate the absorption of TH9507 following pulmonary delivery. Male beagle dogs were administered TH9507 by intratracheal dry powder insufflation and subcutaneous injection at doses of approximately 375 and 38 μg/kg, respectively. In a separate study, male and female dogs received 100 μg/kg intravenously. Blood samples were collected at selected sampling times after dosing and plasma levels of TH9507 were measured by radioimmunoassay. The bioavailability by the inhaled route was 41% relative to subcutaneous dosing, with an absolute bioavailability estimated at 13%. No significant difference was observed for the terminal half-life of TH9507 after intratracheal (39 min) and subcutaneous (26 min) administrations. The mean residence time (MRT) was greater following intratracheal administration (74 min versus 52 min; P
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2004.02.012