Hemoperfusion for imipramine overdose: elimination of active metabolites

The serum concentrations of imipramine and its pharmacologically active metabolites were followed during resin hemoperfusion for imipramine overdose. The initial serum concentration of 2-hydroxy-imipramine plus 2-hydroxy-desipramine was 13.3% of the total tricyclic antidepressant level (imipramine + desipramine + hydroxymetabolites). Despite high extraction ratio (greater than or equal to 0.75) and clearances (130--180 mL/min) for both imipramine and its metabolites, the calculated amount of drug removed was small. Only 0.91% of the estimated dose ingested was removed as imipramine, 0.52% as desipramine, and 0.33% as hydroxylated metabolites. While the hydroxylated metabolites of imipramine may contribute to its toxicity, it is unlikely that the small amount removed can explain reports of apparent clinical benefit from hemoperfusion.