Fluorocarbon aerosol propellants IV: Pharmacokinetics of trichloromonofluoromethane following single and multiple dosing in dogs

An intravenous dosage form of trichloromonofluoromethane, a common aerosol propellant, was formulated in polyethylene glycol 400 for single and multiple dosing to unanesthetized dogs. A three-compartment open model was proposed for disposition of this compound in dogs with average half-lives of 3.2, 16, and 93 min for three disposition phases. This finding is contrary to several reports where blood levels were monitored for shorter periods. A computer analysis of tissue compartment distribution following a single dose showed that about 2 hr was required to achieve pseudodistribution equilibration, following which more than 90% of the dose remaining in the body was retained in tissue compartments. Pulmonary clearance and volumes of distribution were calculated considering first-pass effect through the lung. The volume of distribution was approximately six times the body weight in terms of blood concentrations, and about 30% of the propellant was cleared from blood passing through the lung in each cycle. Disposition of propellant followed dose-independent kinetics after multiple dosing, and accumulation in tissues continued for a much longer period, resulting in high tissue compartment levels.