EPINEPHRINE DELIVERY TO THE ISOLATED PERFUSED RABBIT LUNG

SUPONG AKESIRIPONG, Purdue University

Abstract

Tracheobronchial administration of epinephrine has been recommended in cardiopulmonary resuscitation as an alternative to intravenous epinephrine. The pulmonary absorption of epinephrine administered via intratracheal, intrabronchial, and intrapulmonary solutions and by an aerosol mist were investigated using an isolated perfused rabbit lung as an animal model. These routes of administration were compared to intravascular administration to characterize the absorption patterns of epinephrine. In patients undergoing cardiopulmonary arrest, cardiac output may be less than 10% of normal. Therefore, reduced perfusion flow rates were also used to simulate blood flow in patients under CPR conditions. The results demonstrated that epinephrine was absorbed slowly from the lung into the perfusion medium, reaching peak concentrations in 16-46 minutes. Tracheobronchial instillation led to variable absorption patterns as exhibited by the peak concentrations, which varied from 0.3 (mu)g/ml to 7.1 (mu)g/ml. Intrabronchial administration led to higher epinephrine levels in the perfusate, though the rate of absorption was somewhat delayed with both administration techniques. Intrapulmonary instillation caused a localized distribution of epinephrine solution in the lung, leading to considerable variability in the drug absorption. Epinephrine was absorbed more quickly from an aerosol mist than from tracheobronchial instillation, reaching peak concentration within five minutes after dosing. The nebulized mist seemed to be the most suitable dosing method among the tracheobronchial dosing techniques. There was no relationship between the perfusate flow rate and epinephrine bioavailability. The concentration-time profiles obtained from this study suggested that epinephrine was eliminated in a non-linear fashion described by the Michaelis-Menten kinetics.

Degree

Ph.D.

Subject Area

Pharmaceuticals

COinS