PHARMACOEPIDEMIOLOGY AND DRUG UTILIZATION Tricvclic antide~ressants in red J cells and plasm& Correlation with impaired htraventricular conduction 1 acute overdose Objective: Tricyclic antidepressant levels in red blood cells and plasma in acute overdose and their asso- ciation with cardiotoxicity were studied. Metho&: This was a prospective study in 15 patients with acute tricyclic antidepressant overdose. Tricy- clic antidepressant parent compounds and metabolites were measured in red blood cells and plasma, and tricyclic antidepressant levels were correlated with ECG indexes of toxicity. Results: Plasma levels of the parent compounds were higher than their red blood cell levels on admission (mean & SD, 691 2 409 and 337 & 220 nglml, respectively). Admission metabolite levels were higher in red blood cells than in plasma (264 + 180 and 190 k 164 nglml, respectively). QRS duration and the red blood cell levels of the metabolites were significantly correlated at the time of admission (r = 0.77,~ < 0.01), as well as at 6 to 10 hours (r = 0.74,~ < 0.01). Cmlwions: In acute overdose, a shift of tricyclic antidepressants fiom plasma to red blood cells and increased levels of red blood cell metabolites reflect tissue redistribution of the drug. Tricyclic antide- pressant red blood cell metabolites are the best markers for impaired intraventricular conduction. (CLIN PHARMACOL THER 1993;54:219-27.) Yona Amitai, MD," Timothy Erickson, MD, Eugenia J. Kennedy, PharmD, Jerrold B. Leikin, MD, Daniel 0. Hryhorczuk, MD, MPH, Jerrold Noble, MD, Paul K. Hanashiro, MD, and Henri Frischer, MD, PhD Chicago, Ill. From the Departments of Pharmacology and Medicine, Rush- Presbyterian St. Luke's Medical Center, Rush University, the Departments of Emergency Medicine, University of Illinois1 Mercy Hospital, Cook County Hospital, Mt. Sinai Hospital, and Lutheran General Hospital. Supported in part by Chicago Community Trust, Toxikon Consor- tium, Chicago, Ill. Received for publication Oct. 19, 1992; accepted April 30, 1993. Presented in part at the American Association of Clinical Toxicol- ogyIAmerican Association of Poison Control Centers, Tucson, Ariz., September 1990. Reprint requests: Henri Frischer, MD, PhD, Rush-Presbyterian St. Luke's Medical Center, Rush University, 1753 West Congress Parkway, Chicago, IL 60612. "On sabbatical leave from the Department of Pediatrics, Hadassah Hospital, Mt. Scopus, Jerusalem, Israel. Copyright O 1993 by Mosby-Year Book, Inc. 0009-9236/93/$1.00 + 0.10 1311148261 Management of patients with acute tricyclic antide- pressant (TCA) overdose requires close monitoring. The significance of plasma levels of TCA agents and their correlation with clinical effects have been ques- tioned.'-' Because TCA agents are extensively distrib- uted in tissues, their determination in red blood cells may have an advantage over plasma levels in reflect- ing tissue concentrations and clinical effects. Matuzas et a ~ . ~ reported that red blood cell TCA levels corre- lated better than plasma TCA levels with the clinical response to depression. Red blood cell levels have not been previously reported in TCA overdose. The ECG is used routinely to monitor patients with acute TCA overdose. The cardiotoxic effects of these agents in- clude intraventricular conduction disturbance with 219