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.