The serum concentrations of imipramine and its pharmacologically active metabolites were followed during resin hemoperfusion for imipramine overdose. The initial serum concentration of 2-hydroxyimipramine plus 2-hydroxy-desipramine was 13.3% of the total tricyclic antidepressant level (imipramine + desipramine + hydroxymetabolites). Despite high extraction ratios (≥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.
Bibliographical noteFunding Information:
Supported by Grant No. 20852 while Dr DeVane was a Fellow, Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo.