Metabolic interaction between ethanol, high-dose alprazolam and its two main metabolites using human liver microsomes in vitro

Abstract Alprazolam is widely used as a short-acting antidepressant and anxiolytic agent and its effect appears at very low doses while ethanol is used as a social drug worldwide. Sometimes, toxic interactions occur following combined administration of these two drugs. In this study we have investigated the interaction between ethanol and high-dose alprazolam using human liver microsomes in vitro . The interaction effects between ethanol and alprazolam were examined by a mixed-function oxidation reaction using a human liver microsomal preparation. Alprazolam and its two main metabolites (α-hydroxyalprazolam: α-OH alprazolam, 4-hydroxyalprazolam: 4-OH alprazolam) were measured by HPLC/UV. The production of 4-OH alprazolam, one main metabolite of alprazolam, was weakly inhibited by higher dose of ethanol, but not α-OH alprazolam. These results using a human liver microsomal preparation show that the production of 4-OH alprazolam is weakly inhibited by ethanol but not α-OH alprazolam. Toxic levels may be reached by simultaneous administration of ethanol and high-dose alprazolam.