Date of Completion

Spring 5-1-2014

Thesis Advisor(s)

John Morris

Honors Major

Doctor of Pharmacy

Disciplines

Circulatory and Respiratory Physiology | Medical Toxicology | Other Pharmacy and Pharmaceutical Sciences | Respiratory System

Abstract

The following series of studies investigates the elimination and uptake trends of halothane, acetone, and ethanol vapors in the airways of C57BL/6J mice. These vapors were chosen because they span a wide range of solubilities, as indicated by their blood-air partition coefficients, and are not associated with any significant airway metabolism or reactivity with tissue substrates in vivo. Mice were exposed to a homogeneous vapor mixture containing a 1:1:1 ratio of halothane, acetone, and ethanol at relative concentrations of approximately 10 ppm. Exposure studies were performed with mice in two states, conscious and deceased, in order to provide control against adsorption to superficial anatomical features. Elimination rates were measured by recording airborne vapor concentrations at discrete intervals via gas chromatography. Decay constants were obtained through log-linear regression analysis, and were used to calculate clearances and fractional uptake ratios. The average clearance per mouse for halothane, acetone, and ethanol vapors was 20.9 ± 1.70 mL/min, 51.9 ± 1.88 mL/min, and 52.2 ± 1.54 mL/min (normalized mean ± standard deviation), respectively. Fractional uptake values for each vapor were, in the same order, 0.238 ± 0.053, 0.589 ± 0.123, and 0.593 ± 0.123. A non-linear relationship between the blood-air partition coefficient and airway extraction was observed, suggesting that vapor solubility is correlated with absorption in a complex manner that requires advanced, highly compartmentalized models to accurately predict.

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