Metabolism and deposition of propanol and acetone vapors in the upper respiratory tract of the hamster

Abstract

While it is thought that local metabolism may enhance nasal deposition of inspired vapors, there have been no studies designed to quantitate this effect. In the current study, deposition of 1-propanol (a metabolized vapor) and acetone (a nonmetabolized vapor) was studied in the surgically isolated upper respiratory tract (URT) of the anesthetized Syrian hamster. The effect of inspiratory flow rate on URT deposition of acetone could be described by a ventilation-perfusion (V-P) model with a nasal perfusion rate of 0.046 ml/min. Theoretical considerations predict that at enzyme saturation, deposition efficiency will be dependent upon the inspired concentration and that URT metabolism rates can be estimated from the concentration-dependence data. A concentration dependence on propanol deposition efficiency was observed at a flow rate of 200 ml/min, but not at 38 or 71 ml/min. At a flow rate of 200 ml/min, an apparent URT metabolism rate of 3.8 μg/min (95% confidence limits 0.5–7.1 μg/min) was estimated. In vitro studies on nasal tissue homogenates provided metabolism rates of approximately 2 μg/min, values which did not differ significantly from, and therefore, were in reasonable agreement with, the estimates from the deposition studies. After correction for the effect of metabolism, URT propanol deposition could be described by the V-P model with a nasal perfusion rate of 0.050 ml/min. This value did not differ significantly from that observed in the acetone studies. Thus, deposition of both propanol and acetone in the URT of the Syrian hamster could be described by the V-P model. Metabolism appeared to enhance deposition of propanol, but the effect was only observed at the highest inspiratory flow rate, suggesting that nasal ventilation rates may influence the overall metabolic fate of this vapor.