Amoxapine in human overdose

Amoxapine, a tricyclic antidepressant, is metabolized to 8-hydroxyamoxapine and 7-hydroxyamoxapine. There are few reports on the metabolism of this drug and correlation of clinical symptoms in overdose patients. Five such patients admitted to the Emergency Unit of the University of Cincinnati Hospital were studied. Clinically, all had seizures and evidence of altered cardiac function. The amounts of the parent drug and the 7- and 8-hydroxy metabolites were measured and, in all cases, the parent and 8-hydroxy metabolite were present in both urine and serum. In contrast, the 7-hydroxyamoxapine was found in trace amounts in the serum of only two patients, but in the urine of all the patients observed. These observations were confirmed by gas chromatographic/mass spectroscopic analysis. The pattern of metabolism was analogous to that found in patients on maintenance doses of the drug. In two overdose patients, it was possible to monitor the levels as a function of time. The elimination curve of parent and metabolite was first order with a half-life of 8.5 to 15.0 and 48 hr, respectively.