Pulmonary delivery of anorectic oxyntomodulin in rats: food intake suppression, reduced body weight gain and pharmacokinetics.

Abstract

BACKGROUND:

Oxyntomodulin (OXM1-37) is an anorectic gut-secreting peptide with a promise to treat obesity, but its needle-free delivery has yet to be successful.

RESULTS:

Pulmonary delivery of OXM1-37, but not its C-terminal octapeptides, caused dose-related, transient 4-6 h food intake suppression in rats. At 0.5 mg/kg, its 30-38% food intake suppression led to 46% reduction in body weight gain by day 8. Its lung absorption was fast, elevating the systemic level rapidly, yet the bioavailability was low at 13%. In the brain, twofold neuronal c-fos activation was seen in the hypothalamus arcuate nucleus and brainstem area postrema.

CONCLUSION:

Pulmonary delivery is a promising needle-free systemic delivery option for OXM1-37 to treat obesity, as enabling effective lung absorption and brain interaction.

• Authors: Priya P Nadkarni, Matthew S Halquist, H Thomas Karnes, Richard M Costanzo, Masahiro Sakagami
• Journal: Therapeutic delivery (Ther Deliv) Vol. 6 Issue 3 Pg. 297-306 (Mar 2015) ISSN: 2041-5990 [Print] England
• PMID: 25853306 (Publication Type: Journal Article)

Chemical References

• Appetite Depressants
• Oxyntomodulin

Topics

• Animals
• Appetite Depressants (administration & dosage, pharmacokinetics)
• Brain (metabolism)
• Drug Delivery Systems
• Eating (drug effects)
• Lung (metabolism)
• Male
• Oxyntomodulin (administration & dosage, pharmacokinetics)
• Rats
• Rats, Sprague-Dawley
• Weight Gain (drug effects)