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 greater than kidney greater than serum greater than fat greater than spleen greater than duodenum greater than lung greater than 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.