Integrated phase I pharmacokinetics and pharmacodynamics of epinephrine administered through sublingual film, autoinjector, or manual injection.

Background: Epinephrine is the first-line treatment for anaphylaxis and is administered through intramuscular or subcutaneous injection. AQST-109, a sublingual film containing the prodrug epinephrine, was developed as an alternative delivery method for treating severe allergic reactions, including anaphylaxis.

Objective: To compare the pharmacokinetics (PK) and pharmacodynamics (PD) of epinephrine after the administration of AQST-109 with those of epinephrine delivered by manual intramuscular injection and epinephrine autoinjectors.

Methods: Data were integrated from 2 randomized, open-label, phase I crossover trials that evaluated the PK and PD of epinephrine in 54 healthy volunteers. They had no previous medical conditions and were delivered either AQST-109 12 mg or 0.3 mg EpiPen, 0.3 mg generic EpiPen, 0.3 mg Auvi-Q, and 0.3 mg manual intramuscular injection.

Results: AQST-109 yielded comparable epinephrine PK and exposure to both manual intramuscular injections and epinephrine autoinjectors. The median time to maximum concentration (Tmax) for AQST-109 was 15 minutes, compared with EpiPen (10 minutes), generic EpiPen (15 minutes), Auvi-Q (30 minutes), and manual intramuscular injection (50 minutes). There was also an early, rapid, and consistent increase in systolic blood pressure, diastolic blood pressure, and heart rate after the administration of AQST-109.

Conclusion: AQST-109 delivered epinephrine with PK and PD results within the bracketed range of approved intramuscular products. AQST-109 has promise as an innovative, needle-free, nondevice, portable, and orally delivered alternative for first-line treatment of type I allergic reactions, including anaphylaxis.