Epinephrine absorption after different routes of administration in an animal model

Background: the administration of epinephrine is the most important initial treatment in systemic anaphylaxis. Purpose: we wanted to determine the rel ationship between the route of epinephrine administration and the rate and extent of epinephrine absorption. Methods: in a prospective, randomized, fi ve-way crossover study in rabbits, we measured plasma epinephrine concentra tions before, and at intervals up to 180 min after epinephrine administrati on by intramuscular or subcutaneous injection, or by inhalation, with intra venous epinephrine and intramuscular saline as the positive and negative co ntrols, respectively. Results: maximum plasma epinephrine concentrations we re higher, and occurred more rapidly, after intramuscular injection than af ter subcutaneous injection or inhalation, and were 7719 +/- 3943 (S.E.M.) p g/mL at 32.5 +/- 6.6 min, 2692 +/- 863 pg/mL at 111.7 +/- 30.8 min and 1196 +/- 369 pg/mL at 45.8 +/- 19.2 min, respectively. Intravenous injection of epinephrine resulted in a plasma concentration of 3544 +/- 422 pg/mL at 5 min, and an elimination half-life (t(1/2)) of 11.0 +/- 2.5 min. In the sali ne control study, the endogenous epinephrine concentration peaked at 518 +/ - 142 pg/mL. Conclusion: in this model, absorption of epinephrine was signi ficantly faster after intramuscular injection than after subcutaneous injec tion or inhalation. The extent of absorption was satisfactory after both in tramuscular and subcutaneous injections. Neither the rate nor the extent of absorption was satisfactory after administration by inhalation. Copyright (C) 1999 John Wiley & Sons, Ltd.