PHARMACOKINETICS AND PHARMACODYNAMICS OF ARS-1 AND MANUAL INTRAMUSCULAR INJECTION IN SUBJECTS WITH/WITHOUT ALLERGIC RHINITIS

Abstract

<h3>Introduction</h3> The intranasal (IN) epinephrine spray (ARS-1) is an investigational, needleless alternative to epinephrine injection for patients with severe systemic allergic reactions. <h3>Methods</h3> This single-dose, partially randomized crossover phase 1 study investigated the pharmacokinetics (PK) and pharmacodynamics (PD) of ARS-1 2 mg IN (under normal conditions and with induced rhinitis) and manual intramuscular (IM) injection (0.3 mg and 0.5 mg) in subjects with seasonal allergies. IRB approval was obtained for this study. <h3>Results</h3> Thirty-six subjects were included in the study. Mean C_max values (pg/mL) with ARS-1 (491) and ARS-1 with rhinitis (309) were higher than or similar to those for 0.3 mg (283) or 0.5 mg (452) IM injection. Median t_max values (minutes) were lowest with ARS-1 (20.0) and ARS-1 with rhinitis (6.00) compared with either IM dose (both 45.00). Mean E_max for systolic blood pressure (SBP; mmHg), diastolic blood pressure (DBP; mmHg), and heart rate (HR; bpm) with ARS-1 (20.8, 10.0, 18.5 respectively) and ARS-1 with rhinitis (15.0, 7.15, and 10.8) was higher than or comparable to that of 0.3 mg IM (13.4, 5.26, and 11.1) and 0.5 mg IM (15.2, 5.69, 13.6). Similarly, the mean AUEC_last in SBP, DBP, and HR for both ARS-1 groups was higher than or similar to either IM group. <h3>Conclusion</h3> PK and PD parameters with ARS-1 2 mg with and without allergic rhinitis were higher/better or comparable with those of 0.3 or 0.5 mg IM injection.