Fluorocarbon aerosol propellants XI: Pharmacokinetics of dichlorodifluoromethane in dogs following single and multiple dosing.

A three-compartment open model was proposed for the disposition of dichlorodifluoromethane in dogs with average half-lives of 1.47, 7.95, and 58.5 min for the three disposition phases. This proposal is contrary to several studies that monitored blood levels for a shorter period. An analysis of the tissue compartment distribution following a single dose showed that about 1.5 hr was required to achieve pseudodistribution equilibration, following which more than 90% of the dose remaining in the body was retained in the tissue compartments. The pulmonary clearance and volumes of distribution were calculated considering the first-pass effect through the lungs. The volume of distribution after reaching pseudodistribution equilibrium was approximately 10 times the body weight in terms of the blood concentration, and about 68% of the propellant was cleared from the blood passing through the lungs in each cycle. Disposition of the propellant followed dose-independent kinetics after multiple dosing. No volatile metabolites were detected in the blood using GC.