Chatchawan Srisawat,1,2 Rattana Pipitpreecha,3 Weerawadee Chandranipapongse,4 Somruedee Chatsiricharoenkul,4 Piyapat Pongnarin,4 Supornchai Kongpatanakul,4 Apirom Laocharoenkiat,5 Orathai Jirapongsananuruk,3 Nualanong Visitsuntorn,3 Pakit Vichyanond3

1 Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
2 Siriraj Metabolomics and Phenomics Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
3 Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
4 Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
5 Pharmacy Department, Siriraj Hospital, Bangkok, Thailand

Abstract

Background: Epinephrine 5 mg administered via the intranasal (IN) route was shown to be bioequivalent to epinephrine 0.3 mg administered via the intramuscular (IM) route in our preliminary study.
Objective: To investigate the pharmacokinetics and pharmacodynamics of IN and IM epinephrine absorption in a larger group of healthy adults (n = 12).
Methods: Each subject was administered IN saline, IN epinephrine (5 mg), and IM epinephrine (0.3 mg) on 3 separate days. Plasma epinephrine levels were determined using liquid chromatography-tandem mass spectrometry.
Results: IN epinephrine administration showed significant systemic absorption compared to IN saline control with the areas under the curve (AUC0-180 min) of 4.4 (4.9) ± 4.0 and 0.2 (0.5) ± 0.3 ng.min/mL, respectively; the values are mean (median) ± standard deviation. IN epinephrine absorption was about 0.5-fold that of IM epinephrine (AUC0-180 min 10.0 (9.2) ± 8.6 ng.min/mL), but the difference was not statistically significant (p = 0.16). The mean peak epinephrine concentration and the time to reach it were also not significantly different between the IN and IM routes. The corresponding values were 120 pg/mL and 41 min for IN, and 209 pg/mL and 41 min for IM, respectively.
Conclusion: The systemic absorption of IN epinephrine 5 mg was significantly different from the control IN saline and about 0.5-fold that of IM epinephrine 0.3 mg. Although epinephrine administration via the less invasive IN route is safe and feasible, further investigations are necessary to achieve an adequate and consistent systemic absorption comparable to that of the conventional IM injection.
Key words: epinephrine, intranasal administration, intramuscular injection, pharmacokinetics, pharmacodynamics, anaphylaxis