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Evaluation of novel particles as an inhalation system for GLP‐1
Author(s) -
LeoneBay A.,
Grant M.,
Greene S.,
Stowell G.,
Daniels S.,
Smithson A.,
Villanueva S.,
Cope S.,
Carrera K.,
Reyes S.,
Richardson P.
Publication year - 2009
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2009.01096.x
Subject(s) - glucagon like peptide 1 , inhalation , pharmacodynamics , dosing , medicine , diabetes mellitus , pharmacology , intraperitoneal injection , pharmacokinetics , insulin , pancreas , endocrinology , type 2 diabetes , anesthesia
Aim: The feasibility of administering native glucagon‐like peptide 1 (GLP‐1) as GLP‐1 Technosphere® Inhalation Powder for diabetes therapy has been demonstrated in a rat model. Methods: GLP‐1 Technosphere Inhalation Powders containing 5, 10 and 15% GLP‐1 were prepared and administered to healthy female Sprague–Dawley rats and to male Zucker diabetic obese rats. Rats received a single dose of GLP‐1 Technosphere Powder by pulmonary insufflation. GLP‐1 pharmacokinetic and pharmacodynamic responses were measured. Results: Maximum circulating GLP‐1 concentrations were achieved at ∼10 min after dosing with detectable levels at 40 min. In a food consumption study, Sprague–Dawley rats receiving GLP‐1 Technosphere Powder once‐daily consumed less food than control rats for up to 24 h after dosing. Cumulative food consumption was decreased approximately 10% after 78 h. In an intraperitoneal glucose tolerance test, Zucker diabetic fatty rats receiving 2 mg GLP‐1 Technosphere Powder (0.3 mg GLP‐1) by pulmonary insufflation exhibited lower glucose concentrations and higher insulin concentrations than control rats. Pancreatic evaluations showed no differences in apoptotic index or cell proliferation of β‐cells. In addition, a dose‐related increase in insulin expression within the pancreas was observed. Conclusions: These data demonstrate the feasibility of administering native GLP‐1 as GLP‐1 Technosphere Inhalation Powder for diabetes therapy.