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

Abstract

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 P 450 (CYP) enzyme has been implicated in the metab. of several psychotropic drugs, and has clin. 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, CYP2C19, CYP2D6 and CYP3A4 using human liver microsomes. Amoxapine inhibited both CYP2D6 and CYP3A4 with apparent Ki values of 25.4 and 41.3 micro M, resp. The calcd. Ki value for amoxapine was higher than the common therapeutic concn. 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 obsd. in this study and the therapeutic amoxapine concn. in the blood, we conclude that amoxapine would not cause the severe drug-drug interaction mediated by CYP enzymes. [on SciFinder (R)]