Irreversible protein binding of 14C-imipramine in rats in vivo

Forty-eight hours after a single dose of ¹⁴C-imipramine to rats, ¹⁴C-radioactivity could be measured in the following organs: liver > kidney > serum > fat > spleen > duodenum > lung > muscle and brain. Liver microsomes contained the main part of radioactivity derived from ¹⁴C-imipramine.After exhaustive extraction, only the proteins of liver, kidney, spleen, lung and serum contained measurable amounts of radioactive labeling. The greatest amount of ¹⁴C-imipramine irreversibly bound to proteins was detected in liver microsomes.The question, as to whether the irreversible protein binding of imipramine, if it occurs during therapy, results in toxic side-effects, is discussed.