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A novel nasal powder formulation of glucagon: toxicology studies in animal models

Overview of attention for article published in BMC Pharmacology and Toxicology, January 2015
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Title
A novel nasal powder formulation of glucagon: toxicology studies in animal models
Published in
BMC Pharmacology and Toxicology, January 2015
DOI 10.1186/s40360-015-0026-9
Pubmed ID
Authors

Frederick E. Reno, Frederick E. Reno, Patrick Normand, Kevin McInally, Sherwin Silo, Patricia Stotland, Myriam Triest, Dolores Carballo, Claude Piché

Abstract

Glucagon nasal powder (GNP), a novel intranasal formulation of glucagon being developed to treat insulin-induced severe hypoglycemia, contains synthetic glucagon (10 % w/w), beta-cyclodextrin, and dodecylphosphocholine. The safety of this formulation was evaluated in four studies in animal models. The first study evaluated 28-day sub-chronic toxicology in rats treated intranasally with 1 and 2 mg of GNP/day (0.1 and 0.2 mg glucagon/rat/day). The second study evaluated 28-day sub-chronic toxicology in dogs administered 20 and 40 mg of formulation/dog/day (2 and 4 mg glucagon/dog/day) intranasally. A pulmonary insufflation study assessed acute toxicology following intra-tracheal administration of 0.5 mg of GNP (0.05 mg glucagon) to rats. Local tolerance to 30 mg of GNP (equivalent to 3 mg glucagon, the final dose for humans) was tested through direct administration into the eyes of rabbits. There were no test article-related adverse effects on body weight and/or food consumption, ophthalmology, electrocardiography, hematology, coagulation parameters, clinical chemistry, urinalysis, or organ weights, and no macroscopic findings at necropsy in any study. In rats, direct intra-tracheal insufflation at a dose of 0.5 mg of GNP/rat (0.05 mg glucagon/rat) did not result in adverse clinical, macroscopic, or microscopic effects. In dogs, the only adverse findings following sub-chronic use were transient (<30 s) salivation and sneezing immediately post-treatment and mild to moderate reversible histological changes to the nasal mucosa. Daily dosing over 28 days in rats resulted in mild to moderate, unilateral or bilateral erosion/ulceration of the olfactory epithelium, frequently with minimal to mild, acute to sub-acute inflammation of the lamina propria at the dorsal turbinates of the nasal cavity in 2/10 males and 3/10 females in the high-dose group (0.2 mg glucagon/day). These lesions resolved completely over 14 days. Histological examination of tissues from both sub-chronic studies in dogs and rats revealed no microscopic findings. In rabbits, clinical observations noted in the GNP-treated eye and/or surrounding areas included ≥1 of the following: clear discharge, red conjunctiva, partial closure, and swelling of the peri-orbital area, which correlated with erythema and edema noted during ocular observations and grading. The studies reported here revealed no safety concerns associated with GNP in animal models. Studies published earlier have highlighted the local safety profile of intranasally administered cyclodextrins (a component of GNP). The choline group, the phosphate group, and the saturated 12-carbon aliphatic chain that are present in the dodecylphosphocholine excipient used in GNP are all present in the phospholipids and lecithins seen ubiquitously in mammalian cell membranes and are unlikely to pose safety concerns; this notion is supported by several studies conducted by the authors that revealed no safety concerns. Taken together, these results suggest that intranasal delivery of GNP holds promise as a future rescue medication for use by caregivers to treat insulin-induced hypoglycemic episodes in patients with type 1 or type 2 diabetes. This novel drug product is well tolerated in animal models.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 2%
Kazakhstan 1 2%
Unknown 50 96%

Demographic breakdown

Readers by professional status Count As %
Researcher 13 25%
Student > Bachelor 6 12%
Student > Master 6 12%
Student > Ph. D. Student 5 10%
Other 4 8%
Other 8 15%
Unknown 10 19%
Readers by discipline Count As %
Medicine and Dentistry 12 23%
Pharmacology, Toxicology and Pharmaceutical Science 10 19%
Agricultural and Biological Sciences 6 12%
Chemistry 5 10%
Biochemistry, Genetics and Molecular Biology 3 6%
Other 7 13%
Unknown 9 17%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 April 2016.
All research outputs
#3,938,023
of 7,615,205 outputs
Outputs from BMC Pharmacology and Toxicology
#116
of 185 outputs
Outputs of similar age
#145,001
of 267,040 outputs
Outputs of similar age from BMC Pharmacology and Toxicology
#6
of 9 outputs
Altmetric has tracked 7,615,205 research outputs across all sources so far. This one is in the 28th percentile – i.e., 28% of other outputs scored the same or lower than it.
So far Altmetric has tracked 185 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.5. This one is in the 28th percentile – i.e., 28% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 267,040 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 35th percentile – i.e., 35% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 9 others from the same source and published within six weeks on either side of this one. This one has scored higher than 3 of them.