Mesa Science Associates and Bryn Pharma Publish Second Pre-Clinical Study of a New Approach to Treating Anaphylaxis
The second in a series of three studies measured the pharmacokinetic and heart rate effects of intranasal epinephrine in dogs.
April 24, 2020
Mesa Science Associates Inc. (MSA) and Bryn Pharma LLC published the findings from the second of three (3) pre-clinical studies conducted in beagle dogs. These studies establish that epinephrine is readily absorbed when administered intranasally and has advantages over an intramuscular injection of epinephrine. The pre-clinical study was managed by MSA and was conducted at MRI Global Laboratories in Kansas City, MO. The study was funded by Bryn Pharma LLC of Raleigh, NC. The study was published Pharmacology Research and Perspectives and is entitled Intranasal Epinephrine in dogs: Pharmacokinetic and heart rate effects.
The second study found that epinephrine administered intranasally was well-tolerated and had advantages when compared to epinephrine via auto-injector (intramuscularly). Intranasal epinephrine administration resulted in a more rapid increase in plasma epinephrine concentration within the first five minutes and produced less increases in heart rate over time when compared to intramuscular injection.
This study involved single doses of intranasal epinephrine given to dogs in doses of 2, 3, 4, 5, 10 and 20 mg. Intramuscular administration of epinephrine was given at doses of either 0.15 or 0.3 mg to the bicep of the dogs using an autoinjector. Three plasma samples were collected before dosing, and after administration at the intervals of 1, 5, 10, 15, 20, 30, 60, and 90 minutes. Electrocardiogram measurements were also used to monitor and record the heart rates at the same intervals. No anesthesia was required for administration of the doses. Increasing intranasal dosing from 2 to 20 mg resulted in a dose-related increase in plasma concentrations of the drug. No significant adverse effects were noted in the dose range of 2 to 10 mg. An intranasal dose of 2 mg produced plasma levels that were similar to those observed with 0.15 mg given by intramuscular administration. Similarly, 4 and 5 mg intranasally resulted in plasma levels that closely approximated the intramuscular administration of 0.3 mg.
Dogs are an advantageous species for clinical translation (pre-human trials) because of the similarities in the nasal environment of dogs and humans. These include similar nasal volume, dimension, surface area, and clearance. During the course of the three canine studies no animals we injured and at the conclusion of the studies all animals were adopted into forever homes.
The overall study offers an alternate route of administration for epinephrine, via the nostril, reducing the anxieties that come along with an auto-injector and the associated hypodermic needle injection. There are known advantages of intranasal administration, but the literature regarding its use is limited. Intranasal administration of epinephrine could lead to increased usage versus an auto-injector, with less hesitation for use in patients with severe allergies.
Anaphylaxis is a serious and sometimes life-threatening allergic reaction where the immune system overreacts to an allergen by releasing histamines that cause allergy symptoms. In severe cases if anaphylaxis isn’t properly treated, it can be fatal. Rates of such reactions have increased over the last 20 years and are usually treated by administering epinephrine into a muscle with an auto-injector.
Michael Mesa, CEO of Mesa Science Associates, is anticipating the publication of the last of three (3) studies this spring. These pre-clinical studies preceded human studies which were started in 2019 and are planned for completion over the coming summer. The planned clinical studies will further investigate intranasal epinephrine pharmacokinetic and pharmacodynamic effects. Mr. Mesa stated that “These study results are the cumulation of effective partnering with Bryn Pharma and Mesa Science Associates and is just another example of the exceptional achievements that have resulted from effective collaboration between our two companies on this program.” He also noted that “during the conduct of these studies no animal was injured and all study animals were adopted into forever homes.”
In addition to the pre-clinical studies, MSA continues to provide support for Bryn Pharma nasal product development activities including device activities, identification of a contract fill and finish source, and coordination with the fill and finish source for Chemistry, Manufacturing and Controls activities. MSA also utilizes its extensive list of pharmaceutical experts to provide advice on a variety of manufacturing, clinical, quality, technical and scientific issues.
Mesa Science Associates is a pharmaceutical product development company located inside the Frederick Innovation and Technology Center Inc. (FITCI) in Frederick, MD. The mission of the company is to provide technical and scientific expertise to researchers from all aspects of the drug, drug delivery and product development community, including researchers from government, academia, as well as private entities.