The journal of allergy and clinical immunology. In practice · 2024
Pharmacokinetic and Pharmacodynamic Profile of Epinephrine Nasal Spray Versus Intramuscular Epinephrine Autoinjector in Healthy Adults.
СтатьяКлиническое исследование I фазыСравнительное исследованиеРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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Greenhawt Matthew, Lieberman Jay, Blaiss Michael, Bernstein David I, Oppenheimer John, DuBuske Lawrence, Fleischer David, Dworaczyk David A
Аннотация
BACKGROUND: Standard of care for anaphylaxis treatment is intramuscular (IM) epinephrine. An epinephrine nasal spray (ENS) is under development as an alternative form of administration.
OBJECTIVE: To compare the pharmacokinetic and pharmacodynamic (PD) profile of 13.2 mg ENS with 0.3 mg IM epinephrine autoinjector.
METHODS: Data from 4 open-label phase 1 crossover studies conducted in healthy adults were pooled to determine the pharmacokinetic and PD profile of a single 13.2 mg ENS dose delivered by 2 consecutive sprays of 6.6 mg each in opposite (n = 224 doses) or the same nostril (n = 75 doses) compared with the 0.3 mg IM autoinjector (n = 215 doses). Each participant served as their own control. Blood samples and vital signs were collected predose and at multiple intervals from 0 to 360 minutes postdose.
RESULTS: ENS rapidly increased the plasma epinephrine concentration, with levels that were overall greater than IM autoinjector. Median (range) time to maximum plasma epinephrine concentration with ENS opposite nostrils, ENS same nostril, and IM autoinjector was 25.1 (1.3-362.1), 20.1 (3.0-120.2), and 20.0 (1.0-121.3) minutes, respectively. The area under the plasma concentration-time curve for 0 to 360 minutes was significantly higher with ENS than with the IM autoinjector (geometric mean ratio [90% CI], 155% [140%-172%] with ENS opposite nostrils, 159% [138%-182%] with ENS same nostril). The PD effects on heart rate and blood pressure were similar in pattern and magnitude among all 3 treatment groups.
CONCLUSIONS: ENS rapidly achieved plasma epinephrine levels greater and more sustained than the IM autoinjector and with a similar PD effect.
OBJECTIVE: To compare the pharmacokinetic and pharmacodynamic (PD) profile of 13.2 mg ENS with 0.3 mg IM epinephrine autoinjector.
METHODS: Data from 4 open-label phase 1 crossover studies conducted in healthy adults were pooled to determine the pharmacokinetic and PD profile of a single 13.2 mg ENS dose delivered by 2 consecutive sprays of 6.6 mg each in opposite (n = 224 doses) or the same nostril (n = 75 doses) compared with the 0.3 mg IM autoinjector (n = 215 doses). Each participant served as their own control. Blood samples and vital signs were collected predose and at multiple intervals from 0 to 360 minutes postdose.
RESULTS: ENS rapidly increased the plasma epinephrine concentration, with levels that were overall greater than IM autoinjector. Median (range) time to maximum plasma epinephrine concentration with ENS opposite nostrils, ENS same nostril, and IM autoinjector was 25.1 (1.3-362.1), 20.1 (3.0-120.2), and 20.0 (1.0-121.3) minutes, respectively. The area under the plasma concentration-time curve for 0 to 360 minutes was significantly higher with ENS than with the IM autoinjector (geometric mean ratio [90% CI], 155% [140%-172%] with ENS opposite nostrils, 159% [138%-182%] with ENS same nostril). The PD effects on heart rate and blood pressure were similar in pattern and magnitude among all 3 treatment groups.
CONCLUSIONS: ENS rapidly achieved plasma epinephrine levels greater and more sustained than the IM autoinjector and with a similar PD effect.