Fluorocarbon Aerosol Propellants IV: Pharmacokinetics of Trichloromonofluoromethane following Single and Multiple Dosing in Dogs

Abstract

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.