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 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 38microg/kg, respectively. In a separate study, male and female dogs received 100microg/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 (39min) and subcutaneous (26min) administrations. The mean residence time (MRT) was greater following intratracheal administration (74min versus 52min; P<0.01). These data indicate that the delivery of the TH9507 by the inhalation route may provide a suitable alternative to subcutaneous injection.
Jansen
Mendel
M
Quadrant Drug Delivery Limited, 1 Mere Way, Ruddington, Nottingham NG11 6JS, UK.
Darby
Ian
I
Abribat
Thierry
T
Dubreuil
Pascal
P
Ferdinandi
Eckhardt S
ES
Hardy
John G
JG
D000042:Absorption; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D004285:Dogs; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives; D006207:Half-Life; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007442:Intubation, Intratracheal; D008297:Male; D010455:Peptides / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D011863:Radioimmunoassay
D010455:Peptides; D013007:Growth Hormone-Releasing Hormone; C479538:tesamorelin