Chlorimipramine-induced phospholipidosis: biochemical and pharmacokinetic observations in the rat

Subchronic treatment of rats with the antidepressant drug chlorimipramine produced an accumulation of phospholipids (PL) which was particularly evident in lung and to a lesser extent in liver and spleen. The overall increase in PL was mostly sustained by phosphatidylcholine. Both chlorimipramine and its demethylated metabolite were preferentially accumulated by lung reaching levels of about two orders of magnitude higher than those found in plasma. A significant correlation between the percentage increase in phospholipid contents and drug metabolite tissue level was evidentiated.