The Inhibitory Effect of Amoxapine on Cytochrome P450 Enzyme Activity in Human Liver Microsomes

Amoxapine is a tricyclic antidepressant used for the treatment of psychotic depression. Psychotic depression is generally refractory to medical treatment and plural medicines are usually prescribed concurrently. The cytochrome P450 (CYP) enzyme has been implicated in the metabolism of several psychotropic drugs, and has clinical relevance relating to drug-drug interactions between psychotropic drugs and other common medicines. This study investigated the effects of amoxapine on the activities of CYP1A2, CYP2C9, CYP2C 19, CYP2D6 and CYP3A4 using human liver microsomes. Amoxapine inhibited both CYP2D6 and CYP3A4 with apparent Ki values of 25.4 and 41.3 ACM, respectively. The calculated Ki value for amoxapine was higher than the common therapeutic concentration range in plasma. Our study also revealed that inhibition of CYP2D6 and CYP3A4 enzyme activity by amoxapine is based on a competitive mechanism. Based on the Ki values observed in this study and the therapeutic amoxapine concentration in the blood, we conclude that amoxapine would not cause the severe drug-drug interaction mediated by CYP enzymes.