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.
D000335:Aerosol Propellants / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D000336:Aerosols / Q000378:metabolism*; D000818:Animals; D005617:Chlorofluorocarbons, Methane / Q000008:administration & dosage / Q000378:metabolism*; D003201:Computers; D004285:Dogs; D005466:Fluorocarbons / Q000097:blood; D006207:Half-Life; D007275:Injections, Intravenous; D007700:Kinetics; D008168:Lung / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D013997:Time Factors
D000335:Aerosol Propellants; D000336:Aerosols; D005617:Chlorofluorocarbons, Methane; D005466:Fluorocarbons