Sublingual epinephrine film rivals intramuscular injection delivery times, concentrations
Click Here to Manage Email Alerts
LOUISVILLE, Ky. — A sublingual film delivered sufficient concentrations of epinephrine to the blood faster than autoinjectors, according to a study presented at the American College of Asthma & Immunology Annual Scientific Meeting.
A PharmFilm technology called DESF delivers the AQST-109 (Aquestive Therapeutics) epinephrine pro-drug during anaphylaxis without an injection or any concerns for safety or tolerability as well, John Oppenheimer, MD, FAAAAI, clinical professor of medicine at UMDNJ Rutgers and a Healio Allergy/Asthma Peer Perspective Board Member, and colleagues wrote in the study.
“Studies have shown that patients and their parents are resistant to carrying autoinjectable epinephrine and have fears regarding use of needles in some cases,” Oppenheimer told Healio.
Also, current injectable delivery methods come with pitfalls including lack of autoinjector availability at the time of anaphylaxis, inadequate patient education, failure to administer in a timely manner and accidental administration, the researchers wrote.
“Thus, a smaller alternative form of epinephrine without a needle would likely be used to fill present gaps and unmet needs,” Oppenheimer said.
To determine what the final dose and formulation of this sublingual administration would be, the EPIPHAST randomized, open-label, three-part, adaptive design crossover study compared seven configurations of DESF and their pharmacokinetics and pharmacodynamics in 16 healthy volunteers per formulation and dosage, along with a control group of 16 who received a 0.5 mg intramuscular injection of epinephrine.
DESF formulation 5 was the fastest, the researchers found, achieving clinically meaningful blood concentrations with median times to maximum concentration of 15 minutes at a 10 mg dose and 22.5 minutes at a 12 mg dose. Mean maximum concentration values with this formulation included 285 pg/mL for the 10 mg dose and 268 pg/mL for the 12 mg dose.
Overall, the researchers said that the DESF formulations can deliver epinephrine and achieve sufficient blood concentrations faster than current epinephrine autoinjectors with higher doses.
Also, AQST-109 provides a distinct pharmacokinetic profile relative to 0.3 mg injected epinephrine that is consistently faster with similar peak exposure levels. Specifically, formulation 5 at 12 mg provided the best results, the researchers continued.
“This present abstract builds upon prior research demonstrating fast action,” Oppenheimer said.
The results of the 12 mg dose were comparable to those of a first-in-human study and to those that have been reported for intramuscular injections of epinephrine, the researchers wrote. Also, the researchers called the adverse event profiles and tolerability similar across all the formulations and dosages.
Early and transient increases in systolic blood pressure with DESF were consistent with the known pharmacologic effects of epinephrine and similar to those found with the EpiPen (Pfizer), the researchers found. Increases in heart rate were transient as well.
“The next step includes further validation in larger numbers,” Oppenheimer said.