Pharmacokinetics of quinacrine after intrapleural instillation in rabbits and man

Quinacrine was given by intrapleural instillation or intravenous infusion to 10 rabbits. The uptake of quinacrine from the pleural space was rapid and complete. The mean absorption half-life was approximately 7 min and the mean bioavailability was slightly in excess of 100%. Similar absorption characteristics generally applied in man, in a pilot study on four patients. In three of them, peak quinacrine plasma concentrations were reached that were far above the normal therapeutic range. Known systemic side-effects of quinacrine comprise CNS stimulation, toxic psychosis and convulsions. In view of the high bioavailability and the large doses used for pleural sclerosing (pleurodesis) in patients, neurological disease and psychiatric disturbances that predispose to CNS toxicity should be considered as contraindications to intrapleural quinacrine.