Inhibition of mirtazapine metabolism by Ecstasy (MDMA) in isolated perfused rat liver model.
Daru June 28, 2017 Sanaz Jamshidfar, Yalda H. Ardakani, Hoda Lavasani et al. 5 citations
MDMA (ecstasy) inhibits two key liver enzymes, CYP2D6 and CYP3A4, that metabolize the antidepressant mirtazapine (MRZ). In an isolated perfused rat liver model, animals given MDMA before MRZ showed 80% higher parent drug concentrations and 50% lower concentrations of both major metabolites (8-hydroxymirtazapine and N-desmethylmirtazapine) compared to controls. The area under the curve for the parent drug increased by 50%, while those for the metabolites decreased by 70% and 60%, respectively. Hepatic clearance dropped by 20% and intrinsic clearance by 60%. These findings indicate that ecstasy consumption can substantially alter MRZ metabolism, potentially affecting its efficacy and safety.